Database for Annotation, Visualization and Integrated Discovery 2.1
National Institute of Allergy and Infectious Disease
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HRas proto-oncogene, GTPase(HRAS) HRas proto-oncogene, GTPase(HRAS) Related Genes Homo sapiens
CHROMOSOME 11,
CYTOBAND 11p15.5,
ENSEMBL_GENE_ID ENSG00000174775,
GENERIF_SUMMARY The Tg.AC (v-Ha-ras) transgenic mouse model provides a reporter phenotype of skin papillomas in response to either genotoxic or nongenotoxic carcinogens., The Tg.Ac (v-Ha-ras) mouse model was not overly sensitive and possesses utility as an adjunct to the battery of toxicity studies used to establish carcinogenic risk., immunohistochemical analysis reveals a protective effect of H-ras expression mediated via apoptosis in node-negative breast cancer patients, molecular dynamics simulations to show that Ras, a monomeric G protein, can generate mechanical force upon hydrolysis, Point mutations were identified in DNA from two of the 115 normal individuals. Both mutations resulted in an amino acid substitution at position 12 in H RAS., H-Ras/mitogen-activated protein kinase pathway inhibits integrin-mediated adhesion and induces apoptosis in osteoblasts, H-Ras mutations at the binding site for the GTP nucleotide ring in a human multiple myeloma line leads to transformation and factor-independent cell growth, HRAS genes are biallelically expressed in multiple fetal and adult tissues both in humans and in mice, overexpression of PPARalpha or the c-Ha-ras transgene is not associated with the liver tumorigenesis induced by DEHP in rasH2 mice, steady-state structure of the switch I region of the protein in both the inactive GDP-bound conformation as in the active GTP-bound conformation., Ha-ras mutations detected in HPV-induced cervical intraepithelial neoplasia grade II and invasive squamous cell carcinoma, Results demonstrate the close relationship between Ha-ras expression level and sensitization of 5-flurouracil (5-FU)-treated cells., using fragments of the human c-Ha-ras gene containing 8-hydroxyguanine (8-OH-G) in codon 12, evidence for the highly complex biochemical events leading to activation of the oncogene, the human c-Ha-ras proto-oncogene product does not influence the androgen-dependence of prostate carcinogenesis due to the probasin-mediated SV40 T antigen., Ras activates the MAP kinase cascade through simultaneous dual effector interactions, When mutated, causes hepatocarcinogenesis in transgenic mice., complete loss of p53 is a prerequisite for collaborating with activated Ha-ras to promote bladder tumorigenesis, H-ras mutations have a role in malignant transformation of aerodigestive spindle cell carcinoma, a domain of Rap1 acts dominantly on COOH-terminal lipid modification of Ha-Ras, which has been considered to be essential and sufficient for the plasma membrane localization, Changes in flexibility upon protein-protein complex formation of H-Ras & the Ras-binding domain of C-Raf1 have been investigated using the molecular framework approach FIRST and molecular dynamics simulations of in total approximately 35 ns length., ras gene alterations have a specific and early role in the development of follicular type of thyroid tumors in Taiwan., Myc rescued cell growth inhibition induced by Ras, RAS appears to be a pejorative prognostic factor in terms of survival in NSCLC globally, in ADC and when it is studied by PCR., No significant correlations were found between mutations in colorect cancer., H-Ras-specific activation of Rac-MKK3/6-p38 pathway has a role in invasion and migration of breast epithelial cells, the mechanism of O2*-mediated Ras guanine nucleotide dissociation is similar to that of NO/O2-mediated Ras guanine nucleotide dissociation, Ras exists in (at least) two conformational states identifiable by nuclear magnetic resonance spectroscopy, We found mutations in p53, K-ras, and BRAF genes in 35%, 30%, and 4% of tumors, respectively, and observed a minimal or no co-presence of these gene alterations., RAS-MEK-ERK1/2 signaling pathway can sensitize cells to TRAIL-induced apoptosis by up-regulating DR4 and DR5, reduced Ras activation in cells harbouring the Hepatitis C virus subgenomic replicon, K-ras mutations are found in plasma after colorectal tumor resection, the mechanism for Ras-mediated down-regulation of Par-4 is by promoter methylation, Ras isoforms have distinct and separate cellular and subcellular distribution that may persist even in the malignantly transformed state in pancreatic disease, In this study, we probe the cellular and molecular mechanisms of RAS-mediated transformation., HRAS oncogene could play an important role in the development of cervical cancer, in addition to the presence of HPV, by reducing the G1 phase and accelerating the G1/S transition of infected cells, N-Ras(L61) transformed cells lack a G0-G1 arrest upon TGF-beta treatment due to absence of p27., Ras activity regulates Fbw7-mediated cyclin E proteolysis; impaired cyclin E proteolysis is a mechanism through which Ras mutations promote tumorigenesis., RIG1 exerts inhibitory effect at the level of Ras activation, which is independent of Ras subtype but dependent on membrane localization of RIG1. It may be mediated through downregulation of Ras levels and alteration of Ras subcellular distribution., studies provide evidence for the existence of human-specific mechanisms that resist Ras/MEK/ERK-mediated transformation, in primary fibroblasts stabilization of Ras protein by ROS and ERK1/2 amplifies the response of the cells to growth factors and in systemic sclerosis represents a critical factor in the onset and progression of the disease, growth factor-induced, Ras-mediated changes of keratinocyte shape may be an important mechanism that determines the speed of wound epitheli, Germline mutations in HRAS perturb human development and increase susceptibility to tumors., Incidence of K-ras mutation and frequencies of COX-2 and gastrin overexpression are high in laterally spreading granular and protruded type colorectal tumors., We conclude that in wild-type cells, endogenous Ras does not need to be prenylated to be active., IL-24 is a member of IL-10 family of cytokines, and it signals through two hetorodimeric receptors, whose expression is also upregulated by ras oncogenes, K-ras mutation was found in 29% of sporadic adenocarcinomas respectively and in 0% and 22% of the 9 HNPCC cases., Expression of constitutively active Galpha(q)Q209L in cells inhibited Ras activation of the PI3K/Akt pathway but had no effect on Ras/Raf/MEK [MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) kinase] signalling, activation of the PI3K/AKT pathway replaced Ras once tumors formed, although other effectors were still activated independently of Ras, presumably by factors provided upon the establishment of a tumor microenvironment, APC and K-ras, but not CTNNB1 mutations have roles in regulation of expression of hMLH1 in sporadic colorectal carcinomas, Oncogenic RAS activity is directly responsible for OPCML promoter hypermethylation & epigenetic gene silencing. Elevation of the RAS signaling pathway may play an important role in epigenetic inactivation of OPCML in human epithelial ovarian cancer., Analysus if 2502 patients with acute myeloid leukemia at diagnosis for NRAS mutations around hot spots at codons 12, 13, and 61 and correlation of the the results with cytomorphology, cytogenetics, other molecular markers, and prognosis., Ras induces ErbB4 receptor phosphorylation in a non-autocrine manner and this activation depends on multiple Ras effector pathways and on ErbB4 kinase activity., Our data suggest that mutations of PTPN11 as well as RAS play a role in the pathogenesis of not only myeloid hematological malignancies but also a subset of RMS malignancies, Interplay and transmission of structural information between the switch regions are important factors for Ras function. They propose that initiation of GTP hydrolysis sets off the separation of the Ras/effector complex., the H-RAS 81T --> C polymorphism may induce aneuploidy through overexpression of the active p21 isoform of H-RAS, The IGFBP3, hRas, JunB, Egr-1, Id1 and MIDA1 genes were up-regulated in psoriatic involved skin compared with uninvolved skin., intracellular generation of NO* by nNOS leads to S-nitrosylation of H-Ras, which interferes with Raf-1 activation and propagation of signalling through ERK1/2, In 239 Thai adult AML cases, 35 RAS mutations were found in 32 cases (13%) predominantly classified as M1/M2 (53%) followed by M4/M5 (38%). Ten cases were positive for NRAS codon 12, 11 for NRAS codon 61, 13 for NRAS codon 13, and one for KRAS codon 13., Activating RAS mutation is a pivotal molecular lesion that is implicated in the pathogenesis of AML and MDS., Ras mutations were significantly more frequent in inv(16) than in t(8;21) subset (36 versus 8%, P=0.001)., NF1 is a novel regulator of RAS-induced signals in primary vascular smooth muscle cells, There is a signaling loop between Ras-dependent MAPK cascade activation and p73 function., histone deacetylase inhibitor sodium butyrate induces G1/S phase arrest in E1A + Ras-transformed cells through down-regulation of E2F1 activity and stabilization of beta-catenin, Review. An alternative splice form of c-H-ras, called p19ras, is a positive regulator of p73beta via Mdm2. Implications for this previously unidentified means of regulation are discussed in light of tumor suppression and are extended to p53 and p63., K-ras mutations were observed in 68/182 (37.4%) cases of colorectal cancer., ras may be involved in early stages of larynx carcinogenesis and may be activated by other mechanisms different from mutations, such as epigenetic events, Targeted activation of a human oncogenic-ras transgene in rat pancreas can induce carcinomas correspondent to human pancreatic ductal adenocarcinomas., These findings indicate that mechanical strain causes ROS-dependent S-glutathiolation of Ras at Cys118, leading to myocyte hypertrophy via activation of the Raf/Mek/Erk pathway., The entire Ras/Raf/MEK/ERK pathway is activated by intracellular acidosis, indicating that the initiating acid sensor is found at the level of Ras or above., Down-regulation of MIP-1 alpha was not observed following FGFR3 inhibition in MM cells with RAS mutations implicating RAS-MAPK in MIP-1 alpha regulation, Ras and c-Myc play important roles in the up-regulation of nucleophosmin/B23 during proliferation of cells associated with a high degree of malignancy, thus outlining a signaling cascade involving these factors in the cancer cells., Three unrelated Dutch patients with Costello syndrome all have the same mutation, G12S, in HRAS., High prevalence of CIMP-high and K-ras mutations in G-LST, especially in the proximal colon, could strongly suggest that G-LST appearance is associated with a unique carcinogenic pathway., analysis of H-RAS, K-RAS and N-RAS expression in acute myeloid leukemia, Ras expression in cervical keratinocyte cell lines containing stably replicating extrachromosomal HPV-16 consistently diminished anchorage-independent growth (AI), reduced E6 and E7 expression, and caused p53 induction in these cells., Somatic mosaicism for an HRAS mutation causes Costello syndrome., Activation of Ras plays a critical role in modulating the expression of both CXCL10 and CXCR3-B, which may have important consequences in the development of breast tumors through cancer cell proliferation., The hydrolysis of guanosine triphosphate (GTP) by p21(ras) (Ras) has been modeled by using ab initio type quantum mechanical-molecular mechanical simulations. The minimum energy reaction path is consistent with a 2-step mechanism of GTP hydrolysis., Neurofibromin-deficient mouse embryonic fibroblasts (MEFs) and human NF1 tumor cells were more resistant than neurofibromin-expressing cells to apoptosis mediated by two survival pathways, HRAS mutations represent independent but cooperating events to uniparental disomy during embryonic rhabdomyosarcoma development., The activation of HRAS was inhibited by 25.1% or 81.4% in cells cotransfected with wild-type or Golgi-targeted RIG1, respectively., Taken together, the observations indicate that both H-Ras(G12V) and K-Ras4B(G12V) activates non-conventional and perhaps unique effector pathways to induce cytoplasmic vacuolation in glioblastoma cells., Ras and Ral mediate BCR-controlled activation of JUN/ATF2 and NFAT transcription factors, Ras is able to promote monocyte lineage selection via PKC and PDK1., Transfection of U266 cells with constitutively activated H-Ras (Q61L) attenuated ERK1/2 inactivation and dramatically diminished the lethality of statins + UCN-01 regimen., One female patient exhibiting the distal phalangeal creases had a mutation in the HRAS gene., K-ras mutations may play a less important role in the tumorigenesis of ovarian serous tumor of the Chinese patients., The subcellular distribution of K-Ras is driven by electrostatic interaction of the polybasic region of the protein with negatively charged membranes., We identified two known activating and two novel germline HRAS mutations in four patients with an unusual form of congenital myopathy histologically charactered by an excess of muscle spindles., Study identified Crk adapter proteins, Rac1 and H-Ras, but not RhoA or Cdc42 as crucial components of the Helicobacter pylori CagA protein-induced phenotype., The evaluation of a large number of actinic keratoses specimens have found a low gene mutation rate in low-graded AK lesions. p53 mutations rather than p16(INK4a) and/or Ha-ras mutations may be an early event in the development of AK to cutaneous SCC., low rate of RAS-RAF mutations (2/22, 9.1%) observed in Spitz melanocytic nevi suggests that these lesions harbor as yet undetected activating mutations in other components of the RAS-RAF-MEK-ERK-MAPK pathway, De novo germline HRAS (G12A) and KRAS (F156L) mutations in two siblings with short stature and neuro-cardio-facio-cutaneous features., In contrast to C-RAF that requires farnesylated H-Ras, cytosolic B-RAF associates effectively and with significantly higher affinity with both farnesylated and nonfarnesylated H-Ras., BCR/ABL-Y177 plays an essential role in Ras and Akt activation and in human hematopoietic progenitor transformation in chronic myelogenous leukemia, Erf provides a direct link between the RAS/ERK signaling and the transcriptional regulation of c-Myc and suggests that RAS/ERK attenuation actively regulates cell fate, No mutations in HRAS was found in pilocytic astrocytomas., H-Ras mutation defines a molecular subtype of oral carcinoma with favourable outcome and unique biology, a potential key role for activated members of ras family genes in terms of their contribution to the development of nasal polyposis as well as to the hypertrophy of adjacent turbinates., Examination of various growth-regulatory pathways suggested that Bmi-1 overexpression together with H-Ras promotes human mammary epithelial cell transformation and breast oncogenesis by deregulation of multiple growth-regulatory pathways., These data show that a RAS mutation that only perturbs guanine nucleotide binding has similar functional consequences as mutations that impair GTP hydrolysis and causes human disease., These findings suggest that the activation of Ras signaling pathways promotes the generation of brain cancer stem-like cells from p53-deficient mouse astrocytes by changing cell fate and transforming cell properties., Four cases of Costello syndrome had an unusually severe phenotype, associated in three cases with two unusual mutations, c.35G>A, p.G12D in two cases and c.34G>T, p.G12C in the other., the results of HRAS, BRAF and MAP2K1/2 mutation screening in a large cohort of patients with CS and CFC, H-Ras interacts with Spry2-binding partners, c-Cbl and CIN85, in a Spry2-dependent manner., V12 H-Ras oncogenic signaling may contribute to anchorage-independent growth and tumorigenesis by promoting the final cleavage furrow ingression during cytokinesis., Trafficking of H-Ras was examined to determine whether it can enter cells through clathrin-independent endocytosis (CIE)., K-ras mutations were detected in only one of the Hungarian cases; Eight of 19 (42.1%) Japanese cases were MSI-high (presence of novel peaks in more than one of the five loci analyzed), whereas only 1 of 15 (6.7%) Hungarian cases was MSI-high (P = 0.047, study reports on two patients with novel HRAS mutations affecting amino acids 58 (T58I) and 146 (A146V), respectively; both patients show many of the physical and developmental problems characteristic for Costello syndrome, Taken together, these results reveal a novel role for fad24 in the repression of NF-kappaB activity and H-ras-mediated transformation., Some smoking characteristics, i.e. being an ex-smoker, frequency and inhalation, may be associated with risk for colorectal cancer characterized by the wild-type KRAS gene, especially in men., Hras mutation is associated with familial non-medullary thyroid carcinoma, The redox sensitive p21Ras-ERK pathway plays a critical role in sensing and delivering the pro-apoptotic signaling mediated by S-nitrosoglutathione., Results correlate P53 status and mutation site/type with nuclear protein accumulation, clinicopathologic variables and data on K-ras mutations and high-level microsatellite instability., high frequency of mutations in the PIK3CA, HRAS and KRAS genes leads us to believe that dysregulation of the phosphatidylinositol 3-kinase or Ras pathway is significant for the development and progression of penile carcinoma., K-RAS and BRAF mutations are a frequent genetic event in our samples of sporadic papillary and medullary thyroid carcinoma., K-ras and p53 genes are altered in Tamoxifen-associated endometrial carcinoma, Study shows that SOS responds to the membrane density of Ras molecules, to their GTP loading and to the concentration of phosphatidylinositol-4,5-bisphosphate, and that the integration of these signals potentiates the release of autoinhibition., Report extremely weak tumor-promoting effect of troglitazone on splenic hemangiosarcomas in rasH2 mice induced by urethane., RAS signalling may play an important role in neuronal susceptibility to Sindbis virus infection, p19(ras) interaction with p73beta amplifies p73beta-induced apoptotic signaling responses including Bax mitochondrial translocation, cytochrome c release, increased production of reactive oxygen species and loss of mitochondrial transmembrane potential., p21 Ras/Imp regulate cytokine production and migration in CD4 T cells, Presence of K-ras mutations might be associated with lack of response to panitumumab alone and inferior survival in patients with metastatic colorectal cancer., Scribble is an important mediator of MAPK signalling and cooperates with H-ras to promote cell invasion., k-ras may have a role in progression of rectal cancer after resection, K-Ras mutations have a role in treatment outcome in colorectal cancer patients receiving exclusive fluoropyrimidine therapy, Low-penetrant RB allele in small-cell cancer shows geldanamycin instability and discordant expression with mutant ras., HRAS-shRNA could efficiently down-regulate the expression of H-ras, induce apoptosis of SACC-M cells and simultaneously inhibit cell proliferation., Occupational exposure to coking oven emissions increases expression levels of P21 and P53 proteins in peripheral white blood cells., LDLs stimulate p38 MAPKs and wound healing through SR-BI independently of Ras and PI3 kinase, transfection of a promoterless K-ras cDNA resulted in a significant decrease in endogenous K-ras in a dose- and time-dependent manner and induces pancreatic cell apoptosis, This review will summarize the chemical biology of Ras and discuss in more detail the biophysical and structural features of the membrane bound C-terminus of the protein., the H-RAS T81C polymorphism might be a low penetrance gene predisposition factor for gastric cancer in the Chinese population, Ca(2+) may activate Ras signaling pathway by interaction with Ras, providing clues to understand the role of calcium in regulating Ras function in physiological environments., This study revealed S100A8/A9 genes as candidate markers for metastatic potential of breast epithelial cells., The secondary structure of membrane-bound, lipidated Ras is similar to that determined for the nonlipidated truncated Ras protein for the highly conserved G-domain., Hdm2 is expressed in pancreatic cancer cells as a result of activated Ras signaling, and regulates cellular proliferation and the expression of target genes by p53-independent mechanisms., Costello syndrome-associated HRAS mutations result in prolonged signal flux in a ligand-dependent manner, Ras transformation has at least two independent actions to disrupt E-cadherin junctions, with effects to cause both mislocalization of E-cadherin away from the cell surface and profound decrease in the expression of E-cadherin, The increased accumulation of miR-143 inhibits the proliferation of transfected cells, and results in down-regulation of K-ras protein in colorectal carcinoma., RAS mutations may play a greater role in leukemogenesis than currently believed, The oncoprotein Ras is a possible mediator of Tax-induced apoptosis protection and suggest a possible role of Tax in Ras activation., failed to find hRAS mutations in bladder tumor samples, The Snail-p53 binding as the new therapeutic target for K-Ras-mutated cancers including pancreatic, lung, and colon cancers., Women with the NAT2 fast acetylator genotype may exhibit a higher risk of CRC with increased occurrence of K-RAS mutation., Subtle deficits in inhibition and enhanced excitation evoke the interneuronal changes in the synRas transgenic mouse cortex., K-RAS point mutations, and anomalies of p16-RB1-cyclin D pathway could occur before LOH on 10q23 (PTEN) and microsatellite instability during tumor progression., p21(Ras)-mediated survival signaling is regulated by via a PI(3)K-AKT pathway, which is dependent upon both PDK1 and PKCdelta, and PDK1 activates and regulates PKCdelta to determine the fate of cells containing a mutated, activated p21(Ras)., Rho mediates various phenotypes of malignant transformation by Ras and Src through its effectors, ROCK and mDia [review], A single patient with somatic mosaicism for a Costello syndrome causing HRAS mutation is reported. The male-to-male transmission was from father to son., BLNK recruits active H-Ras to the BCR complex, which is essential for sustained surface expression of BCR in the form of the cap and for the signal leading to functional ERK activation, A novel regulatory mechanism whereby turnover of both endogenous and overexpressed H-Ras protein is controlled by beta-TrCP-mediated ubiquitylation, proteasomal degradation and the Wnt/beta-catenin signaling pathway, is reported., These findings support the hypothesis that the Ras/Raf/Mek/Erk pathway may be constitutively active even in pancreatic tumor cells that express wild-type K-ras., EGFR expression and KRAS mutation status is predictive for clinical response to matuzumab +/- paclitaxel in patients with advanced NSCLC., K-ras mutations, significantly associated with the mucin-secreting type of adenocarcinoma, consistently predict lack of response in white patients, Data show that the combination with CA 19-9 assay is useful for detection and prognostic evaluation of pancreatic carcinoma., Alcohol consumption is weakly associated with an increased risk of having a K-ras mutated pancreatic ductal adenocarcinoma, Study provides evidence that p53, binding with Snail, is exported from a K-Ras-mutated cell through a vesicle transport-like mechanism, independently using a p53-nuclear-exporting mechanism., K-ras, EGFR, and BRAF mutations are disproportionately seen in adenocarcinomas of lung with a dominant micropapillary growth pattern compared with conventional adenocarcinoma in our institutional experience., Chronic NF-kappaB activation delays RasV12-induced premature senescence of human fibroblasts by suppressing the DNA damage checkpoint response., Mutation E17K/AKT1 was not detected in the 24 samples of retinoblastoma analyzed. K-RAS mutations were identified in two samples. There were no mutations in any of the other genes analyzed., HRAS mutation may be a marker of Spitz naevus, The median pancreatic cancer survival in K-ras positive group was 7.0+/-2.4 months and in K-ras negative group was 10.0+/-0.6 months, DEP-1 inhibits the RAS pathway by direct dephosphorylation of ERK1/2 kinases, BMI1 collaborates with H-RAS to induce an aggressive and metastatic phenotype with the unusual occurrence of brain metastasis., KRAS does not seem an "a priori" negative factor for TKI-based treatment of NSCLC, results suggest that RAS is an important member in the PI3K-AKT signaling and could play an important role in the tumorigenesis of oral carcinoma., Sorafenib inhibits NSCLC cell growth by targeting B-RAF in cells with wild-type KRAS and C-RAF in those with mutant KRAS., Data show that in the presence of negative feedback, changes in the rate of Ras-c-Raf binding have little effect on ERK activation., Investigated the prevalence of PTPN11, HRAS, KRAS, NRAS, BRAF, MEK1, and MEK2 mutations in a relatively large cohort of primary embryonal Rhabdomyosarcoma (RMS) tumors. HRAS and KRAS were found to be rarely mutated., Findings show that JNK is necessary for oncogenic H-ras-induced, caspase-independent cell death, and that both PI3K and Rac1 activities are required for JNK activation and cell death., Data show that significant K-ras mutation occurs most frequently in the pancreatobiliary regions of patients with AIP., the organophosphorous pesticides parathion and malathion induced malignant transformation of breast cells through genomic instability altering p53 and c-Ha-ras, We noted statistically significant difference in genotype distribution at hexanucleotide locus and at SNP 81 T>C between healthy population and colon cancer patients, Data show that conversion of Ras-expressing keratinocytes from a premalignant to malignant state induced by decreasing E-cadherin function was associated with and required an approximately two to threefold decrease in RalA expression., Results show a cooperative relationship between the expression of Ras and loss of RB in providing a discrete proliferative advantage under physiologically relevant conditions., Data suggest that investigation of the mechanisms of abnormal RAS and phosphoinositide-3 kinase pathway activation in erythroblasts may contribute to the understanding of the molecular pathogenesis of PV., HRAS codon 12 mutation is not a very common event in actinic keratosis or nonmelanoma skin cancers, A single cellular event for mutations arising in male germ cells that show a paternal age effect; screening of 30 spermatocytic seminomas for oncogenic mutations in 17 genes identified 2 mutations in FGFR3 and 5 mutations in HRAS., Silencing of the Lats2 tumor suppressor overrides a p53-dependent oncogenic stress checkpoint and enables mutant H-Ras-driven cell transformation., RAS enables DNA damage- and p53-dependent differentiation of acute myeloid leukemia cells in response to chemotherapy, H-ras expression in immortalized keratinocytes produces an invasive epithelium in cultured skin equivalents, Data show that Myc repressed Ras-induced senescence, and that Cdk2 interacted with Myc at promoters, where it affected Myc-dependent regulation of genes, including those of proteins known to control senescence., Screening for BRAF, RET, KRAS, NRAS, and HRAS mutations, as well as RET-PTC1 and RET-PTC3 rearrangements, was performed on cases of Hashimoto thyroiditis with a dominant nodule, loss of BRCA1 function may contribute to the aggressiveness of Ras-MAPK driven breast cancer with associated increase in levels of cyclin D1 and c-myc, enhanced MAPK activity, angiogenic potential & invasiveness, Exogenous expression of RASSF1A is able to induce growth inhibition effect and apoptosis in nasopharyngeal carcinoma cell lines, and this effect could be enhanced by activated K-Ras., p19 induces FOXO1 that in combination with the G1/S phase delay and hypophosphorylation of both Akt and p70SK6 leads to maintenance of a reversible cellular quiescence state, thereby preventing entry into apoptosis., Features of KRAS mutations in lung cancer and contrast these with the features of EGFR mutations., The identification of mutations outwith previously described hotspot codons increases the K-Ras mutation burden in colorectal tumours by one-third., The present study suggests that the single-clonal convergence of K-ras mutation is associated with the malignant progression of intraductal papillary mucinous neoplasms., In Chinese patients with CRC, EGFR mutations were rare, and K-ras mutations were similar to those of Europeans., Oncogenic K-Ras and its effector Raf1 convert death receptors into invasion-inducing receptors by suppressing the ROCK/LIM kinase pathway, and this is essential for K-Ras/Raf1-driven metastasis formation., JNK2 collaborates with other oncogenes, such as Ras, at multiple molecular levels to promote tumorigenesis, increased binding of DNMT3b to E-cadherin promoter region by K-Ras cause promoter hypermethylation for reduced expression of E-cadherin, leading to the decreased cell aggregation and increased metastasis of human prostate cancer cells., Ras induces ARC in epithelial cancers, and ARC plays a role in the oncogenic actions of Ras, Using lung cell lines expressing oncogenic K-Ras, authors show that NF-kappaB is activated in these cells in a K-Ras-dependent manner and that NF-kappaB activation by K-Ras., maintain colorectal cancer cell proliferation during ERK MAP kinases inhibition, Costello syndrome is a rasopathy caused by germline mutations in the proto-oncogene HRAS., X-ray crystal structure analyses of a series of mutant H-Ras and M-Ras in complex with guanosine 5'-(beta,gamma-imido)triphosphate (GppNHp), representing various intermediate states of the transition, were determined., Leukotriene B(4) BLT receptor signaling regulates the level and stability of cyclooxygenase-2 (COX-2) mRNA through restricted activation of Ras/Raf/ERK/p42 AUF1 pathway, Mutations may predict the biological nature of pulmonary adenocarcinomas and facilitate new therapies., investigation of whether HRAS is involved in development of vestibular schwannomas not associated with an underlying NF2 mutation; no potentially pathogenic HRAS mutations found; conclude that HRAS is not a common cause of vestibular schwannomas, Recent studies on the cooperative molecular mechanisms by which p53 inactivation and oncogenic Ras converge to enhance tumorigenesis., The HRAS1 haplotype enhanced the effect of an APOE haplotype on exceptional survival, and a LASS1 haplotype further augmented its magnitude., H-ras was altered in 22% of the oral squamous cell carcinoma samples from a Serbian population. Statistical association with tumour natural history was poor, indicating high clonal heterogeneity and multiple pathways of carcinogenesis., Abolishing the expression of cyclin D1, Cdk4 or Nek2 in MCF10A human mammary epithelial cells expressing H-Ras(G12V) abrogated Ras-induced centrosome amplification., HBP1 targets P16(INK4A), upregulating its expression and consequently is involved in Ras-induced premature senescence., Mutation analysis of K-ras protooncogene in colorectal adenocarcinomas and polyps in Russian patients, Gene amplification and overexpression of H-ras is the major mechanism that causes drug resistance of 5-8F/Erbitux cells to cetuximab., Data show that p66(Shc) coordinates Ras-dependent control of proliferation and anchorage sensation., The presence of a K-ras mutation in cytology specimens distinguishes pancreatic cancer frm cholangiocarcinomain this study., The homozygous type of major allele TT was more frequent in GC group than ChG group, while the frequencies of heterozygous type TC and homozygous type of minor allele CC were higher in ChG group than GC group., We show the shift of Ras into its "off" conformation, which inhibits the Ras pathway; down-regulation of Ras signaling by changes in the Ras-Raf effector interaction;& down-regulation of Ras signaling pathway by catalyzing GTP hydrolysis., An association exists between TRAIL resistance to apoptosis in human pancreatic and lung cancer cell lines and G12D K-ras(12) mutation., Ras is a key mediator of IL-1beta-induced NF-kappaB and HIF-1alpha activation, under normoxia., We therefore conclude that HRAS mutation analysis may be a useful diagnostic tool to help differentiate between Spitz nevus and Spitzoid melanoma., Conformational states of human rat sarcoma (Ras) protein complexed with its natural ligand GTP and their role for effector interaction and GTP hydrolysis., There are novel p53 mutations in gastric cancer and mutation patterns of p53 and k-ras in the population of the central southern region of China., Ras mutational status is associated with resistance to EGFR inhibitors in colorectal carcinoma., gene expressions were significantly higher in the cancer group and may serve as reliable biomarkers to monitor tumour development and the efficiency of therapy, The frequency of EGFR mutation in Chinese non-small cell lung cancer patients is higher than that in Westerners, but the frequency of K-ras mutation is quite opposite., miR-181a may function as an oral squamous cell carcinoma suppressor by targeting on K-ras oncogene., the implication of H-Ras and NADPH oxidase-generated superoxide production in MMP-13 gene regulation by IL-1beta and TNF-alpha, HRAS1 polymorphism is associated with breast cancer., Cyst fluid K-ras mutation correlates with other markers of aggressive cyst behavior., these data demonstrate that the activation of H-Ras and the downstream molecule Rac1 correlates with EGF-induced breast cancer cell invasion., Ras/Raf/MAPK and RhoA/ROCKII signalling pathways are abnormally activated in eutopic endometrial stromal cells of patients with endometriosis, Taken together, our data indicate that K-Ras mutations are relatively uncommon in cervical cancer but seem to be associated with more advanced tumor stage, increased risk of distant metastases, and poor probability of long-term survival., HRAS1 polymorphism is not associated with breast cancer., findings show activation of H-ras by mutation plays a less frequent role than other genetic events in the development of most transitional cell tumors of the bladder in Kashmiri population, this work identifies the C-terminal HVR, two consecutive proline residues Pro173 and Pro174, as a critical domain that contributes to activation of H-Ras and its invasive potential in human breast epithelial cells., constitutively active H-Ras can confer resistance to anti-EGFR therapy in cancer cells, Novel ectodermal findings were noted in individuals with p.G13C, including loose anagen hair, easily pluckable with a matted appearance, different from the tight curls typical for most Costello syndrome individuals and long eye lashes requiring trimming, RASSF1A has a tumor suppressive effect as a modulator for ROS production induced by oncogenic K-Ras., Data show that the Ras/PI3K/Akt pathway can account for Fyn over-expression in cancers., CDKN2A/ARF, RAS and TP53, but not BRAF, PTEN, MAPK2 or EGFR may have roles in rare salivary gland tumours, HRAS T81C polymorphism is associated with urinary bladder cancer., G-CSF-induced MMP-2 upregulation and invasive phenotype is mediated by Rac1., data demonstrate that SNPs and point mutations observed in HRAS do not change the amino acid sequence, and suggest that the mutations affecting the amino acid sequence may be a rare event in oral carcinomas of the Japanese population., Regulation of Double Strand Break repair by EGFR involves both the NHEJ and HR pathway, and appears to occur in most tumor cell lines regardless of p53 and K-Ras mutation status., A rare case of pancreatic carcinosarcoma in a 48-year-old man in which the sarcomatous component had an identical mutation (G to A transition) at codon 12 of K-ras gene., Genetic K-ras alterations were rather low in the Tunisian population, but further study is necessary to unravel the molecular background of CRC., both EGFR and HRAS mutations are rare events in the carcinogenesis of cutaneous squamous cell carcinoma, and therefore, only a small subgroup of patients will benefit from the screening for mutations, Transformed cells with an activated Ras signaling pathway are therefore particularly susceptible to human cytomegalovirus infection., The H-Ras-ERK-induced and HO-1-mediated pathway could protect renal cancer cells from apoptosis., These results suggest that mutant K-Ras acts in concert with CDK5 and its activators to increase malignant progression, migration, and invasion of pancreatic cancer cells., HRAS mutations and llelic loss of susceptibility loci are associated with familial non-medullary thyroid cancer., identification of an HRAS mutation c.34G>A, predicting a p.G12S amino acid substitution, in the surviving brother of a previously reported sibling pair with Costello syndrome and documentation of same change in autopsy material from his deceased sister, NADPH oxidase NOX4 is a critical mediator in oncogenic H-RasV12-induced DNA-damage response and subsequent senescence., Our findings suggest that the HRAS mutations identified in Costello syndrome (CS) are sufficient to cause oncogene-induced senescence and that cellular senescence might therefore contribute to the pathogenesis of CS., Solution structure of the state 1 conformer of GTP-bound H-Ras protein and distinct dynamic properties between the state 1 and state 2 conformers., The HRAS G-quadruplexes behave as transcription repressors., the HRAS G12V mutation increased cell migration and invasion, mediated by Rac1, along with the mesenchymal morphology obtained through the epithelial-mesenchymal transition, At least with respect to the binding sites involving the G domain, H-Ras is an excellent model for K-Ras and probably N-Ras as well., Helicobacter pylori infection may increase the expression of c-H-ras p21 early in the process of gastric carcinogenesis, triple-negative cases had a worse prognosis for relapse and death, compared with cases with EGFR, KRAS, or ALK mutations or group B triple-negative cases, Mutations of HRAS are associated with Skin tumors induced by sorafenib., The dermatological features of Costello syndrome, a Ras dysregulation syndrome, share many features with cutaneous paraneoplastic syndromes. This may provide further insight into the role of Ras signalling in cutaneous paraneoplastic syndromes., hRas mutations did not appear to be associated with urothelial carcinoma development after kidney transplantation., Data show that PDEdelta activity augments K/Hras signalling by enriching Ras at the plasma membrane., Mutations in hras proteins are present in benign lichenoid keratosis., RET mutations may have a role in medullary thyroid carcinoma, while BRAF, AKT1, and CTNNB1 do not; the role of HRAS, KRAS, and NRAS mutations are not determined, Data show that MiR-181d may act as a glioma suppressor by targeting K-ras and Bcl-2., EGFR and K-ras mutations frequently occur randomly in multifocal lung adenocarcinomas, The data amassed in last several years indicate that the anti-EGFR antibody is ineffective when KRAS has mutated.[review], No significant influence of age was found on the prevalence of K-ras mutation. Males with pathological changes and females with poorly differentiated tumors displayed GAT as a less common genotype compared with most other prevalence studies., The activating point mutations of HRAS in Costello syndrome shift the balance toward the active, signal transmitting state, resulting in dysregulation of the signaling pathway., Genetic alterations in SMAD4 and K-ras in Serbian patients with endometrial carcinoma., In HRAS, two hotspot mutations in codon 12 and eight new genetic alterations were detected in oral squamous cell carcinoma., Findings indicate that Ras-induced nuclear accumulation of activated MEK1/2 was reliant on downregulation of the spatial regulator Sef., reduced C4ST-1 expression and chondroitin sulfation imbalance mediating the effects of oncogenic HRAS signaling in the pathogenesis of Costello syndrome., A total of 80.8% of Chinese patients with colorectal cancer show variations in microsatellite DNA, p53, APC or K-ras., Generation of cetuximab-resistance in 5-8F/Erbitux cells is associated with amplification and overexpression of the H-ras gene., Activating K-ras mutation is one of the frequently encountered molecular alterations that occur in the pathogenesis of pancreaticobiliary malignancy., we have analyzed the prevalence of somatic mutations in the FGFR3, PIK3CA, AKT1, KRAS, HRAS, and BRAF genes in bladder cancers, H-Ras activity is differently regulated by the various mutant p53 categories in tumor cell lines., EFVPTC 2 patients had RAS mutations., COLD-PCR is a highly sensitive, reliable, and convenient clinical assay for H-ras mutation detection in bladder cancer., Transmission of the mutation underscores its attenuated phenotype compatible with reproduction, The polymorphism of H-ras and L-myc genes is not related to colorectal cancer risk, but there is a synergy between H-ras and L-myc polymorphisms in the development of rectal cancer., GSK3beta plays an essential role in Ras degradation and inhibition of this degradation pathway by aberrant Wnt/beta-catenin signaling may contribute to Ras-induced transformation in colorectal tumorigenesis, molecular, clinical, and pathological findings in patients with mutations predicting HRAS p.Gly12Val, activating RAS somatic mutations leading to mosaicism result in benign Keratinocytic epidermal nevi (KEN) of the skin., H-Ras transformation promotes tumor progression by enhancing growth factor receptor signaling as a result of increased receptor macropinocytosis., Studies indicate that mutations of TP53 and Ras proteins were found in cutaneous squamous cell carcinomas (SCCs) cells., The GTP bound state 1 crystal structures of wild-type H-Ras together with the oncogenic G12V and Q61L mutants., study examined the mutational spectra of Ras isoforms curated from large-scale tumor profiling and found that each isoform exhibits surprisingly distinctive codon mutation and amino-acid substitution biases, The consequence of complex formation is a DiRas3-mediated recruitment and anchorage of C-RAF to components of the membrane skeleton, suppression of C-RAF/B-RAF heterodimerization, and inhibition of C-RAF kinase activity., These results suggest that rs12628 C homozygosis of the HRAS gene may be considered a potential risk factor for melanoma development in the North American population, Mosaicism for HRAS c.37G>C and KRAS c.35G>A mutations was found in two individuals with Schimmelpenning syndrome., ). Abnormal methylation of the HRAS gene may be an early event during urocystic tumorigenesis and may be further used as a cancer biomarker in bladder tissue for early diagnosis and a potential therapeutic target., In advanced NSCLC, the presence of K-RAS mutations identifies a subgroup of patients who do not respond to EGFR-TKI therapy., endogenous IL-1beta play a role in elastin gene upregulation and this upregulation is mediated by the Ras-ERK1/2 pathway in 3D cultures, Upregulation of NKG2D ligands by H-RasV12 increased sensitivity of cells to NK cell-mediated cytotoxicity, A novel interplay between K-ras and H-ras, with possible implications for colorectal carcinogenesis., It was concluded that extracellular kinase-mediated up-regulation of c-myc by K-Ras or B-Raf oncogenes disrupts the establishment of apical/basolateral polarity in colon epithelial cells independently of its effect on proliferation., RAS mutations are frequent events in sporadic medullary thyroid cancer., S-nitrosylation of H-Ras at Cys(118) and the activation of Src kinase are spatiotemporally linked events of the S-nitrosothiol-mediated signaling pathway that occurs at the plasma membrane and at the Golgi., K-Ras mutations were present in 89 patients (32.6%)., possible role of K- ras mutation as an early event in the process of endometrial carcinogenesis in type 1 tumors, HRAS p.G12C and p.G12D mutations found in 2 patients with severe neonatal Costello syndrome., the Ras-PI3K signaling pathway targets specific epigenetic modifications in tumor cells, The mutation frequencies of K-ras genes in Taiwanese CRC patients are very low, which may suggest that they are not the dominant factors for CRC occurrence and prognosis in Taiwanese CRC patients., Ras oncoproteins transfer from melanoma to T cells, including tumor-infiltrating lymphocytes (TILs), and subsequently induce functional effects in the adopting T cells., Results show that postzygotic HRAS mosaicism affects epithelial progenitor cells resulting in mutated cells with variable developmental potential. Nevus marginalis appears to be a manifestation of this., The Ras/MEK/ERK pathway might be activated by VEGF and play a critical role in the angiogenesis of chronic subdural hematoma., The results confirm a strong correlation between activating RAS mutations and nevus sebaceus., The findings confirm the predominance of HRAS mutations in nevus sebaceus (NS) and provide evidence that HRAS and KRAS mutations are sufficient to cause NS without genome instability, LOH, or secondary mutation., Fendiline significantly mislocalizes K-Ras and inhibits K-Ras signaling., HRAS T81C SNP has been found to moderately increase thyroid cancer risk with variant alleles implicated more in follicular thyroid tumors, The absence of K-ras gene mutations questions its role in the pathogenesis of gastric cancer and peptic ulcer disease in Indian patients., The prevalence of RAS mutations in the present series of medullary thyroid cancer (MTC) was 10.1%, and 17.6% when considering only RET-negative cases. RAS mutations were found in MTC tumor tissue but not in peripheral blood indicating their somatic origin, Data suggest that EPI64A and B, which are ubiquitously expressed members of the EPI64 subfamily, inactivate Ras and certain Rabs at the periphery of cells., Approximately 90% of medullary thyroid cancers had mutually exclusive mutations in RET, HRAS, and KRAS, suggesting that RET and RAS are the predominant driver pathways in medullary thyroid cancer., Mutation in HRAS gene is not associated with phenytoin induced gingival overgrowth., mutant K-Ras contributes to the maintenance of the aberrantly high levels of survivin in tumors by regulating its stability, and the ability of mutant K-Ras to induce malignant transformation is, in part, dependent on these high levels of survivin., We suggest that disrupted HRAS reagibility, as we demonstrate for the p.E63_D69dup mutation, is a previously unappreciated molecular pathomechanism underlying Costello syndrome., Phacomatosis pigmentokeratotica is best explained by a postzygotic-activating HRAS mutation in a multipotent progenitor cell that gives rise to both a sebaceous and a melanocytic nevus., Dynamic palmitoylation links cytosol-membrane shuttling of acyl-protein thioesterase-1 and acyl-protein thioesterase-2 with that of proto-oncogene H-ras product and growth-associated protein-43, A correlation between the specific Costello syndrome-causing HRAS mutation and severity of medical problems in the affected individual., The ability of K-Ras to activate MST2 and MST2-dependent apoptosis is determined by the differential activation kinetics of mutant K-Ras and wild type K-Ras., Data suggest that mutations in HRAS are relatively common (6/28 patients, 21%, p.Gln61Arg or p.Gln61Lys substitution) in subjects with partially-encapsulated or well-circumscribed follicular variant of papillary thyroid carcinoma in Boston area., study used NMR to obtain detailed mechanistic data on RAS cycling defects conferred by oncogenic mutations, or full-length RASopathy-derived regulatory proteins, Wild-type copies of HRas, NRas and KRas play unique roles in the context of mutant KRas-driven tumors., HRas signal transduction promotes hepatitis C virus cell entry by triggering the host CD81-CLDN1 complex formation., Data suggest that RAS mutations are infrequent in patients with myelodysplastic syndrome that identify subset of patients with higher WBC count and higher bone marrow blast burden., Endomembrane H-Ras controls vascular endothelial growth factor-induced nitric-oxide synthase-mediated endothelial cell migration., These results implied that nicotinamide might be a potential therapeutic agent for human pancreatic cancer treatment through downregulating SIRT1, K-Ras and P-Akt expression., study elucidates a novel correlation between the tumor suppressor gene p53 and the oncogene Ras in regulating EMT program, and expands the knowledge about the function of p53 in EMT process, This study identifies HRAS mutations in deep penetrating nevi. The presence of HRAS mutations and absence of GNAQ or GNA11 mutations in deep penetrating nevi suggests classification of these nevi within the Spitz rather than the blue nevus category., beta4 integrin rs8669 genotyping may help to identify a subgroup of HER-3-negative, K-RAS wild-type colorectal cancer patients who are more likely to benefit from anti-EGFR treatment., Data suggest that HRAS mutations are associated with sporadic pheochromocytoma and paraganglioma; this study in Sweden identified three new somatic mutations in HRAS exomes (G13R, Q61K, Q61R) exclusively in males with pheochromocytoma/paraganglioma., Data indicate that numerous proteins that are up-regulated in H-ras(G12V) transgenic rat pancreatic ductal adenocarcinoma (PDAC) are also up-regulated in human PDAC; therefore, this rat model can be used for diagnostic biomarkers for this disease., OHT induced K-Ras degradation in breast, colon, glioma, and pancreatic cancer cells., Data suggest a treatment rationale for Src- or Ras-activated cancer., Suggest that activating mutations of EGFR, HRAS, and KRAS contribute to the pathogenesis of human seborrheic keratosis., Tunneling nanotubes connecting B and T cells provide a hitherto undescribed route for the transfer of plasma membrane patches containing, for example, H-Ras from B to T cells., Among 30 breast tumors, 10(33%) had BCSCs with AKT1, HRAS, or PIK3CA mutations. A single mutation was detected in HRAS.Tumors in which BCSCs have defects in PI3K/Akt signaling are significantly more likely to manifest nodal metastases., Data indicate oncogenic HRAS (HRAS(G12V)) as a potent mediator of SLC5A8 silencing in human nontransformed normal mammary epithelial cell lines and in mouse mammary tumors through DNMT1., In silico results showed conformational changes in H-RAS that could influence its activation by Sos and phosphate binding, H-ras is one of the genes targeted by miR-663, These results provide evidence for a role of H-ras oncogene in the metabolic reprogramming of MCF10A cells during early mammary carcinogenesis., Finding of somatic activating HRAS and NRAS mutation in bone, the endogenous source of FGF23, provides the first evidence that elevated serum FGF23 levels, hypophosphatemia and osteomalacia are associated with pathologic Ras activation., the central role of Ras signaling in enamel formation in Costello syndrome patients, 293 cells transformed with H-Ras enhanced Enteric human adenoviruses replication by more than threefold., HRAS mutations confer erlotinib resistance in head and neck squamous cell culture., HRAS p.G12S mutation has a role in causing woolly hair and epidermal nevi, Results suggest that mosaicism for oncogenic HRAS mutations may increase the risk for developing bladder cancer at a young age., HRAS mutations are associated with proliferative thyroid lesions., Data suggest that mutations in HRAS (as seen in Costello syndrome) affect intrinsic kinetic mechanisms of HRAS and alter HRAS-binding characteristics of GTP/GDP, p120GAP (RAS p21 protein activator), and Cdc25 (guanine nucleotide-releasing factor)., Differences in the regulation of K-Ras and H-Ras isoforms by monoubiquitination., Levels of de novo HRAS mutations in the paternal germline affected by intrinsic mutation rate and selfish selection., there were no significant differences between HRAS mutation positive and mutation negative cases of epithelial-myoepithelial carcinomas in terms of age, gender and outcome., PIK3CA mutations/amplification, HRAS mutation, or PTEN loss that likely lead to PI3K pathway activation were identified in 34 of 75 cases (45%) and did not correlate with disease specific survival., Small G proteins Rac1 and Ras regulate serine/threonine protein phosphatase 5 (PP5).extracellular signal-regulated kinase (ERK) complexes involved in the feedback regulation of Raf1., activating mutations in HRAS are involved in sporadic nevus spilus that may progress to melanocytic neoplasms, H-Ras gene analysis identified an hypermethylated CpG island in intron 1 that can affect the DNA-protein interaction modifying RNA polymerase II (RNAPII) activity., H-Ras forms dimers on membrane surfaces via a protein-protein interface., Mutations in Ha-ras gene is associated with liver tumors., Case Report, HRAS mutations play a critical role in the genesis of rhabdomyosarcoma, Ras(V12)-mediated oncogenic transformation induces RRAD epigenetic inactivation, which in turn promotes glucose uptake and may contribute to ovarian cancer, Somatic H-RAS mutations are restricted to a relevant proportion of sporadic pheochromocytoma., Oncogenic HRAS in head and neck squamous cell cancer promotes activation of ERK signaling, which in turn mediates cetuximab resistance, Ras expression negatively regulated the TSH-stimulated CREB phosphorylation but was ineffective on forskolin-stimulated CREB phosphorylation, Our study further suggests that the PLA/AT activity of H-rev107 may play an important role in H-rev107-mediated RAS suppression, Trichilemmomas commonly harboured activating HRAS mutations., In OCCS, missense mutations in HRAS were found in 10 of 79 cases (12.66%), and were significantly associated with tumor grade., BLT2 is markedly up-regulated by oncogenic Ras and promotes epithelial-mesenchymal transition in response to TGF-beta in mammary epithelial cells., Data suggest that H-Ras inhibits TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis through downregulation of surface death receptors DR4/DR5., We present the case of a patient, in whom fetal tachycardia, polyhdramnios and physical characteristics led to an early diagnosis of Costello syndrome., Patients with somatic mutations, especially HRAS-mutations, have a significantly worse prognosis than patients lacking these changes, H-ras-mediated transformation stimulates vesicular emission of this histone-bound oncogene, which may interact with non-transformed cells., Next-generation sequencing identified recurrent mutations in HRAS (Q61R) in 3 of 5 Inverted urothelial papilloma (IUP), described for the first time in this neoplasm., RAS mutations in indeterminate thyroid nodules have a role in follicular variant of papillary thyroid carcinoma, Case Report, acylation state of Ras proteins (H-Ras and N-Ras) controls not only their distribution between the Golgi apparatus and the plasma membrane, but also their distribution within the Golgi stacks., CARD9 regulates H-Ras activation by linking Ras-GRF1 to H-Ras, which mediates Dectin-1-induced extracellular signal-regulated protein kinase (ERK) activation and proinflammatory responses when stimulated by their ligands., human cellular models with inducible expression of c-Myc and H-RasV12 (Ras), two commonly deregulated oncoproteins operating in a functionally connected signaling network, is reported., Phosphorylation of synaptic GTPase-activating protein (synGAP) by Ca2+/calmodulin-dependent protein kinase II (CaMKII) and cyclin-dependent kinase 5 (CDK5) alters the ratio of its GAP activity toward Ras and Rap GTPases., Ecdysoneless and H-Ras expressing human mammary epithelial cells form tumors in NOD/SCID mice., We have demonstrated that clinically achievable concentrations of zoledronic acid and docetaxel cause a reduction in the prenylation of both H-Ras and Rho A and a reduction of protein movement into the membrane., In the presence of Raf1, the RasQ61L mutant has a rigid switch II relative to the wild-type and increased flexibility at the interface with switch I, which propagates across Raf-Ras binding domain., Data indicate that the farnesyl may determine small GTPase K-Ras4B function in different membrane microdomain environments., H-Ras mediates the inhibitory effect of epidermal growth factor on the epithelial Na+ channel, NORE1A allows Ras to qualitatively modify p53 function to promote senescence., MTH1 expression is required for effective transformation of epithelial cells by oncogenic HRAS., The data suggest a role for redox-dependent activation of wild-type KRAS through cysteine 118 in oncogenic HRAS-driven tumorigenesis., Strongly increased HRAS(Gly60Asp) binding to RAF1., ABL phosphorylates tyrosine 137 of H-, K-, and NRAS., The RAS-binding domain of human BRAF protein exhibits allosteric conformational changes upon binding HRAS., RAS-positive thyroid nodules, especially in older individuals, frequently demonstrate a benign phenotype.Cytologically benign nodules, even if RAS-positive, may be candidates for a non-operative observational strategy, Nanoclustering of mutant proteins in plasma membrane dictates downstream effector recruitment, MAPK-activity, and tumorigenic cell proliferation., Expression of flotillin-1 was associated with H-Ras in breast cancer, especially in TNBC (p < 0.001)., HRAS differentially influences iTBS- and PAS-induced LTP., Data show that Ba/F3 cells transformed with mutant HRAS protien indicated equal sensitivity towards Map kinase kinase (MEK) and mTOR serine-threonine kinase (mTOR) inhibition., analysis of HRAS, KRAS and NRAS expression in colorectal tumor cells, Ras.GDP weakly binds to the catalytic but not to the allosteric site of Sos., Phenotypic Screening Identifies Protein Synthesis Inhibitors as H-Ras-Nanocluster-Increasing Tumor Growth Inducers., SHP2 activity is elevated in astrocytes isolated from glioblastoma multiforme-prone H-Ras(12V) knock-in mice., We describe extensively the tumor suppressive and oncogenic roles of miRNAs in regulation of ras oncogenes in Oral squamous cell carcinoma, Endocytosis separates EGF receptors from endogenous fluorescently labeled HRas and diminishes receptor signaling to MAP kinases in endosomes., our data suggest roles for HRAS and EGFR as drivers in a subset of poroma and porocarcinoma.,
OFFICIAL_GENE_SYMBOL HRAS,
OMIM_DISEASE Bladder cancer, somatic, Spitz nevus or nevus spilus, somatic, Nevus sebaceous or woolly hair nevus, somatic, Schimmelpenning-Feuerstein-Mims syndrome, somatic mosaic, Thyroid carcinoma, follicular, somatic, Congenital myopathy with excess of muscle spindles, Costello syndrome,
SP_COMMENT disease:Defects in HRAS are a cause of bladder cancer [MIM:109800]., disease:Defects in HRAS are the cause of congenital myopathy with excess of muscle spindles (CMEMS) [MIM:218040]. CMEMS is a variant of Costello syndrome., disease:Defects in HRAS are the cause of Costello syndrome [MIM:218040]; also known as faciocutaneoskeletal syndrome. Costello syndrome is a rare condition characterized by prenatally increased growth, postnatal growth deficiency, mental retardation, distinctive facial appearance, cardiovascular abnormalities (typically pulmonic stenosis, hypertrophic cardiomyopathy and/or atrial tachycardia), tumor predisposition, skin and musculoskeletal abnormalities., disease:Defects in HRAS are the cause of oral squamous cell carcinoma (OSCC)., disease:Defects in HRAS may be a cause of susceptibility to Hurthle cell thyroid carcinoma [MIM:607464]; also known as Hurthle cell thyroid neoplasia. Hurthle cell thyroid carcinoma accounts for approximately 3% of all thyroid cancers. Although they are classified as variants of follicular neoplasms, they are more often multifocal and somewhat more aggressive and are less likely to take up iodine than are other follicular neoplasms., disease:Mutations which change positions 12, 13 or 61 activate the potential of HRAS to transform cultured cells and are implicated in a variety of human tumors., enzyme regulation:Alternate between an inactive form bound to GDP and an active form bound to GTP. Activated by a guanine nucleotide-exchange factor (GEF) and inactivated by a GTPase-activating protein (GAP)., function:Ras proteins bind GDP/GTP and possess intrinsic GTPase activity., mass spectrometry: PubMed:9020151, mass spectrometry:Includes one nitric oxide molecule PubMed:9020151, PTM:Palmitoylated by the ZDHHC9-GOLGA7 complex. A continuous cycle of de- and re-palmitoylation regulates rapid exchange between plasma membrane and Golgi., PTM:S-nitrosylated; critical for redox regulation. Important for stimulating guanine nucleotide exchange. No structural perturbation on nitrosylation., similarity:Belongs to the small GTPase superfamily. Ras family., subcellular location:Shuttles between the plasma membrane and the Golgi apparatus., subunit:In its GTP-bound form interacts with PLCE1. Interacts with TBC1D10C. Interacts with RGL3 (By similarity). Forms a signaling complex with RASGRP1 and DGKZ. Interacts with RASSF5.,
KRAS proto-oncogene, GTPase(KRAS) KRAS proto-oncogene, GTPase(KRAS) Related Genes Homo sapiens
CHROMOSOME 12,
CYTOBAND 11p15.5, 12p12.1,
ENSEMBL_GENE_ID ENSG00000133703,
GENERIF_SUMMARY It is proposed that lowering the affinity for GTP allows G12D Ras an escape from the oncogenic GTP-bound state, whereas GTP tightly bound to G12V mutant Ras generates a more persistent, potentially oncogenic, signal., Mutations were detected by using allele-specific amplification method., oncogenic levels of mitogen-activated protein kinase (MAPK) signaling of the dinucleotide KRAS2 mutations G12F and GG12-13VC, valine-12 Ki-Ras mutants demonstrated a greater ability to invade Matrigel than cells expressing the aspartate-12 mutant or wild-type Ki-Ras proteins., KRAS2 mutations have been detected in laser-capture microdissected atypical endometrial hyperplasia specimens arising concurrently with endometrial carcinoma., Ras modulates the proliferative response of RSF to TNF-alpha and TGF-alpha, mutations in K-ras have been detected in primary carcinoma of small intestine, Coordinated traffic of Grb2 and Ras during epidermal growth factor receptor endocytosis, K-ras mutations and RASSF1A promoter methylation in colorectal cancer, Multiple K-RAS mutations are frequent both in PC with associated PanIN and in biliary cancers, and indicate that clonally distinct precursor lesions of PC might variably contribute to tumor development., Constitutive activation of NF-kappaB in Ki-ras-transformed prostate epithelial cells, Mutations in APC, Kirsten-ras, and p53--alternative genetic pathways to colorectal cancer. The most common combination of mutations was p53 and APC (27.1%), whereas mutations in both p53 and K-ras were extremely rare., Uncommon mutation types of K-ras may contribute to long term patient survival in pancreatic adenocarcinoma., study performed to determine the status of K-ras-2 in liver angiosarcomas (LAS) from workers occupationally exposed to vinyl chloride, Immunohistochemical staining of p21 appears to be of prognostic value in patients receiving systemic adjuvant chemotherapy for locally advanced bladder cancer., the constitutive activation of Ras might have induced the persistent expression of p21cip1 and p27kip1, and that this induction of p21cip1 and p27kip1 expression possibly caused the cell cycle arrest at the G1 phase., Review, Specific T-cell immunity against Ki-ras peptides in patients with pancreatic and colorectal cancers., acute hyperglycemia-mediated mononuclear cell activation is dependent on activation of ras, p42/p44 mitogen-activated protein kinase phosphorylation, and subsequent NF-kappaB activation, LOH of chromosome 12p was seen in about 50% of human lung adenocarcinomas & large cell carcinomas. Kras2 mutations were seen at codon 12 in about 40% of adenocarcinomas & large cell carcinomas. The wild-type Kras2 is a tumor suppressor of lung cancer., results demonstrate that the mutational status of BRAF and KRAS is distinctly different among histologic types of ovarian serous carcinoma, occurring most frequently in invasive micropapillary serous carcinomas and its precursors, serous borderline tumors, Ki-ras mutations and HGF signaling cooperate to enhance tumor growth by increased duration of MAPK activation and decreased apoptosis in human carcinoma cells., results suggest that carcinogenesis in the biliary tract epithelium in anomalous pancreaticobiliary ductal union (APBDU) is accompanied by multistep genetic mutational events; K-ras gene mutation occurs early in epithelial hyperplasia or metaplasia, The results suggest a potential role for Ca2+/calmodulin in the regulation of K-RasB function., No somatic mutations were identified in either TP53 or KRAS, indicating that disregulation of these genes is not required for leiomyomas development, types of mutations in sinonasal NK/T cell lymphoma in northeast district of China, codon 12 K-ras mutations in lung tumors or sputum samples from 102 lung cancer patients, p21Ras activation is instrumental in FVIIa signal transduction and the FVIIa-dependent activation of p21Ras involves either PKC or Src-dependent mechanisms, depending on the cell type investigated., K-Ras4B polybasic domain or an alternatively prenylated CAAX renders Ras prenylation, Ras-induced Elk-1 activation, and anchorage-independent cell growth farnesyltransferase inhibitor-resistant., Point mutations in Ki-ras gene is associated with colorectal cancers in mexican patients, signaling initiated by activated Ki-ras interferes with the IFN/STAT signaling pathway and modulates the responsiveness of cancer cells to interferons, K-ras mutations may have an effect on proliferation in pancreatic ductal adenocarcinoma, there is an inverse relationship between Kras2 activation and RASSF1A promoter methylation in the majority of human lung adenocarcinomas and large cell carcinomas, BRAF mutations, which are present in a variety of other human cancers, do not seem to be involved in gastric cancer development, KRAS2 mutations were seen in stomach neoplasms., findings indicate the wild-type KRAS allele is occasionally lost in lung cancer and the oncogenic activation of mutant KRAS is more frequently associated with overexpression of the mutant allele than with loss of the wild-type allele in NSCLC development, The positive expression rates of p21 and p53 proteins were 75.0% and 57.3% respectively in pancreatic carcinoma, which were significantly different from those in the normal tissue (P<0.05). p21 and p53 proteins were positively correlated (P<0.05)., Oncogene Protein p21(ras) accumulation was confined to the upper layer of esophageal squamous cell carcinoma., RAS or BRAF mutations are detected in about 32% of all Barrett's adenocarcinomas; the disruption of the Raf/MEK/ERK (MAPK) kinase pathway is a frequent but also early event in the development of Barrett's adenocarcinoma, Detection of P21 may be used as the screening marker for diagnosis of polycyclic aromatic hydrocarbons (PAHs)-related lung cancer related lung cancer, and may supplement the diagnostic value of conventional cytology., Mutations in K-ras gene is associated with malignant melanomas, These studies identify isoprenylcysteine carboxyl methyltransferase as a potential target for reducing the growth of K-Ras- and B-Raf-induced malignancies., Mutant-type [(12)Asp]K-ras4B can enhance the expression of estrogen receptor alpha and beta proteins and their transcriptional activity as a transcription factor in endometrial carcinoma HEC-1A cell line., p21Ras, hSOS1, and p120GAP are not involved in polycystic ovary disease, k-ras has a role in cell death through the p38 MAP kinase pathway in human colonic cancer cells, K-ras mutation may play a role in the malignant transformation of pancreatic ductal cell., ovarian serous cystadenomas do not contain mutations in either BRAF or KRAS genes, K-ras mutations are frequently found in surgical margins in non-small-cell lung carcinoma patients., Results suggest that changes in telomerase activity and K-ras point mutation at codon 12 may be an early event of malignant progression in pancreatic cancer., k-Ras has a role in promoting butyrate-induced apoptosis by inhibiting gelsolin expression, Sensitivity of PNA clamp PCR assay in identifying occult micrometastases in the sentinal lymph nodes of colorectal cancer patients by single-base mutation analysis., H-Ras mediates FucT-VII induction in Jurkat T cells via the activation of the Raf, PI3K, and a distinct, H-Ras-specific effector signaling pathway., K-Ras mutations were found in 80% of pancreatic adenocarcinoma cell lines and 100% of primary tumors. They were all missense mutations of Gly(12) to Val or Asp., Mutations of BRAF or KRAS oncogenes are early events in the serrated polyp neoplasia pathway. CpG island methylation plays a role in serrated polyp progression to colorectal carcinoma., Detection of K-ras mutations in normal colonic mucosa might serve as a high-specificity approach to colorectal cancer., c-Myc antagonized the induction of p21Cip1 mediated by oncogenic H-, K-, and N-Ras and by constitutively activated Raf and ERK2, Co-mutation of p53 and K-ras gene has neither synergic carcinogenesis-promoting effect, nor prognostic effect on rectal cancer., ANCA selectively activates K-ras during induction of a respiratory burst via pathways involving multiple upstream kinases., Simultaneous measurement of K-ras and p16 mutations provides an additional tool in differential diagnosis of chronic pancreatitis and pancreatic adenocarcinoma., comparison with mouse data show a pattern of gene expression indicative of KRAS2 mutation and oncogenic activity, K-ras mutations occur prominently in type 1 and type 2 gastric cancers., Mutations in either the EGFR TK domain or the KRAS gene can lead to lung cancer pathogenesis. EGFR TK domain mutations are the first molecular change known to occur specifically in never smokers., data suggest that mutations of epidermal growth factor receptor (EGFR) and K-RAS genes might separately, but not cooperatively, contribute to lung adenocarcinoma pathogenesis, Activating KRAS2 mutations were found in 82% of lethal metastatic pancreatic neoplasms., The results obtained from the RASCAL studies suggest that Ki-ras mutations might have an effect on survival rate of colorectal cancer patients, and that the specific codon 12 glycine/valine mutation might play a role in the progression of this neoplasia., Specific TP53 mutations in L3 domain alone (only in DFS) or in combination with specific Ki-ras mutations at codon 13 are associated with a worse prognosis in sporadic colorectal cancer., The sequential accumulation of mutations in K-ras drives the transition from normal epithelium through increasing adenomatous dysplasia to colorectal cancer., Mutant human Kras(D12) suppresses IL-18 production in murine colorectal tumor cells, which may contribute to evasion of the local immune system during tumor development, Clinical evidence that suggests a role for K-Ras in the formation of colorectal metastases. (review), controversial link of KRAS mutations in colorectal cancer with chromosomal instability and patient prognosis (review), MUC5AC and MUC2, TFF1 and TFF3, APC and p21 in subsets of colorectal polyps and cancers suggests a distinct pathway of pathogenesis of mucinous carcinoma of the colorectum, Ras mutations do not play a significant role in the pathogenesis of multiple myeloma in the Spanish population, hepatocyte growth factor signaling and Ki-ras oncogene activation have roles in colorectal cancer, mechanistic insights are now possible into how K-Ras contributes to pancreatic ductal carcinogenesis (review), While most aberrant crypt foci do not have adenopolyposis coli mutations, a large proportion has KRAS mutations. (review), The results suggest that oncogenic K-Ras enhances the malignant phenotype and identify the mitogen-activated protein kinase p38 as a target to inhibit oncogenic K-Ras-induced pancreatic tumor cell migration., Allelic loss on 12p12-13 region would influence the KRAS2 expression by reducing the gene-dosage in colon carcinogenesis., Mutation and elevated expression of KRAS2 is associated with the development of testicular germ cell tumors, KRAS has a role in villous growth in colorectal adenomas, Polymorphisms in some insulin-related genes are associated with an increased risk of colon cancer with specific KRAS2 and TP53 mutations, implying a link between these genetic changes and specific mutational pathways in carcinogenesis., Mutations do not confer a growth advantage to somatic heterozygous clusters or maintenance turnover units., Cardio-facio-cutaneous (CFC) syndrome involves dysregulation of the RAS-RAF-ERK pathway., Germline KRAS mutations are a cause of human disease and infer that the constellation of developmental abnormalities seen in Noonan syndrome spectrum is due to hyperactive Ras., Mutations in transfect Ki-ras promote the formation of benign lung tumors and suggest potential targets for the development of novel chemotherapeutic and chemopreventive agents during the early stages of lung tumor progression., These findings suggest that endogenous Nore1B recruits active Ras to the APC-T cell interface and mediates the interaction between Ras and Carma1., Genomic instability may occur on 12p-12-13 of Kras2 gene in the development and progression of colon carcinoma. The high LOH of Kras2 gene may directly influence the transcription and translation of wild type Kras2 gene., K-ras mutations were detected in 70% of neoplastic tissue samples, but no mutated DNA resulted in circulating DNA samples in pancreatic cancers., In 239 Thai adult AML cases, 35 RAS mutations were found in 32 cases (13%) predominantly classified as M1/M2 (53%) followed by M4/M5 (38%). Ten cases were positive for NRAS codon 12, 11 for NRAS codon 61, 13 for NRAS codon 13, and one for KRAS codon 13., Rodent and human tumor cells containing constitutively activated Raf/Raf/MEK/ERK pathways were resistant to mda-5-induced killing., The role of K-ras codon 12 and codon 13 mutations in human papillomavirus virus-associated colon tumors., A nuclease hypersensitive polypurine-A polypyrimidine element within the promoter of the KRAS proto-oncogene regulates transcription., BRAF mutations are as uncommon as KRAS mutations in prostate adenocarcinoma, the combination of an activating mutation of the TSH receptor (T620I) and a mutation of the Ki-RAS (G12C) genes may play an important role in both the hyperfunction of follicular thyroid carcinoma and the carcinogenetic process, In 50 of the 66 primitive colorectal tumor cases at least one significant alteration was identified in Ki-Ras and/or TP53 and/or p16(INK4A) genes., ras may be involved in early stages of larynx carcinogenesis and may be activated by other mechanisms different from mutations, such as epigenetic events, trichostatin A-induced cell death of Ki-Ras-transformed cells is enhanced by inhibition of NF-kappaB, KRAS mutation occurred frequently (26.5%) in adenomas and particularly in adenomas with villous architecture., These data describe a functional association between K-Ras4B and nucleolin, Ki-ras proto-oncogene mutation and p53 gene overexpression is associated with sporadic colorectal adenomas, K-ras mutations are associated with colorectal cancers, analysis of H-RAS, K-RAS and N-RAS expression in acute myeloid leukemia, BRAF, K-ras and BAT26 are expressed in colorectal polyps and stool, Concomitant KRAS and BRAF mutations increased along progression of MSS colorectal cancer, suggesting that activation of both genes is likely to harbour a synergistic effect, Recurrent KRAS codon 146 mutations is associated with human colorectal cancer, 6 haplotype blocks were identified across the KRAS locus in endometriosis patients. No germline variants or differences in SNPs or haplotypes were seen between cases and controls., KRAS and p53 gene mutations, which are rarely simultaneous and are associated with specific DI aneuploid values, do not represent a synergistic evolutionary pathway but may influence mechanisms of chromosomal instability., Phenotypic variability may be related, at least in part, to specific genotypes and possibly reflects the central role of K-Ras in a number of different signalling pathways., These findings suggest that continuous K-Ras activation accelerates cell growth and evokes a feedback system through IGFBP-4/2 to prevent excessive growth., Presence of an oncogenic KRAS allele results in a dynamic physical interaction between endogenous N-RAS and gelsolin that correlates with survival in colorectal cancer cell lines., K-RAS is uniquely oncogenic in the colonic epithelium, though the molecular aspects of its oncogenic contribution are not necessarily conserved across cell lines., data suggest that mutations of the k-ras oncogene may induce activation of ERK1/2 in colorectal carcinoma, RASSF1A methylation was observed in a high frequency in endometrioid endometrial carcinoma whereas K-ras and B-raf mutations were observed in a low frequency, Rna silencing of K-ras(V12) markedly decreased K-ras(V12) gene expression and inhibited cellular proliferation of lung cancer cells., High-resolution melting analysiswill enable screening of gene mutations, such as KRAS to allow appropriate therapeutic choices for patients and accelerate research aimed at identifying novel mutations in human cancer., Urine might be a better resource for detecting K-ras mutation in circulating DNA in patients with colorectal cancer., association between K-ras mutation and smoking in pancreatic cancer patients, Taken together, the observations indicate that both H-Ras(G12V) and K-Ras4B(G12V) activates non-conventional and perhaps unique effector pathways to induce cytoplasmic vacuolation in glioblastoma cells., This pilot study suggests that low-level fractional allelic loss or K-ras mutation in the negative/atypical cytology samples of bile duct with malignant outcome is a representation of morphologically subtle molecular alterations., analysis of oxidative posttranslational modifications of cysteine thiols of p21ras associated with redox modulation, One female patient exhibiting the distal phalangeal creases had a mutation in the KRAS gene., patients having juvenile myelomonocytic leukemia with NRAS or KRAS2 glycine to serine substitution received no chemotherapy, but hematologic improvement was observed during a 2- to 4-year follow up., K-Ras promotes growth transformation and invasion of immortalized human pancreatic cells by Raf and phosphatidylinositol 3-kinase signaling., The wild-type Kras2 gene effectively inhibits the growth of the colonic adenocarcinoma cell line Caco-2., findings show that RASSF1A hypermethylation and KRAS mutations and BRAF mutations are inversely correlated and play an important role in the development of cervical adenocarcinomas, mutational analysis of KRAS, BRAF, and MAP2K1/2 in 56 patients with CFC syndrome; comparison of the genotype-phenotype correlation of CFC with that of Costello syndrome suggest a significant clinical overlap but not genotype overlap., data suggest that BRAF mutations might be present less frequently than KRAS mutations in Greek patients with colorectal carcinomas, Mutations of K-ras and Dpc4 genes can accumulate already in non-malignant, inflammatory pancreatic tissue, suggesting its applicability in monitoring of further destruction of pancreatic tissue and progression into malignancy., KRAS mutations were present in 3 of 16 serrated compared with 14 of 33 non-serrated hyperplastic aberrant crypt foci, Circulating KRAS mutations originate from tumors and are prognostically relevant in lung cancer., KRAS KRAS mutations were observed significantly frequently in bronchial-type tumors, Genetically, the non-polypoid growth type of submucosal invasive colorectal carcinoma shows much less frequent K-ras mutation., c-kit expression is not alternative to BRAF and/or KRAS activation., it is suggested that atypical adenomatous hyperplasia (AAH) could develop by either KRAS or EGFR gene mutation, but AAH harbouring a KRAS gene mutation might not progress further to an invasive cancer, Activated K-ras is associated with non-small cell lung cancer, A KRAS mutation in a baby girl with an early clinical diagnosis of cardio-facio-cutaneous syndrome associated with a large ulcerating hemangioma, is reported., KRAS G34A mutation was relatively common to all classes of specimen, whereas TP53 gene C742T and G818C mutations were significantly more frequent in lichen sclerosus than normal genital skin., study of EGFR, HER2, TP53& KRAS mutations of p14arf expression of non-small cell lung cancers in relation to smoking, study reveals there are differences in the frequencies & types of K-ras & p53 mutations found in pancreatic adenocarcinomas of patients in high-pollution & low-pollution regions in Egypt & suggests that environmental factors may explain these differences, among adenocarcinomas, nonmucinous and mucinous bronchioloalveolar carcinoma components were significantly associated with EGFR and K-ras gene mutations, respectively, In bronchioalveolar carcinoma/adenocarcinoma with bronchioalveolar features mucinous differentiation was significantly correlated with the absence of EGFR mutation and presence of KRAS mutation., In 2 cases of ovarian tumors the same mutations of KRAS occurred in both the atypical proliferative serous (borderline) tumor and the high-grade serous carcinoma component of the tumor, indicating a clonal relationship., EGFR and K-ras mutations may have a role in progression of resected non-small-cell lung cancer, De novo germline HRAS (G12A) and KRAS (F156L) mutations in two siblings with short stature and neuro-cardio-facio-cutaneous features., NSCLC cases with wt- or mutant KRAS, downregulation of EGFR expression was a rare event although upregulation in bone metastases was observed more frequently in wt K-RAS cases., an important relationship between K-ras codon 12 mutations and overall survival in colorectal cancer patients, tobacco does not play a major part in acquisition of K-ras mutations in the pancreatic epithelium; although both smoking & K-ras mutations have important roles in the etiopathogenesis of exocrine pancreatic cancer, the 2 processes may act independently, Mutations in KRAS is associated with colon tumors, oncogenic K-RAS/ERK in pancreatic adenocarcinoma facilitates TGFbeta-induced transcriptional down-regulation of the tumor suppressor PTEN in a SMAD4-independent manner, combined with screening of K-ras mutations and allelic losses of tumor suppressors p16 and DPC4 represents a very sensitive approach in screening for pancreatic malignancy., KLF6 and p53 mutations are involved in the development of nonpolypoid colorectal carcinoma, whereas K-ras and B-raf mutations are not, Kras mutant lung cancer patients have a significantly worse prognosis than wild-type patients., The majority of colorectal and gastric cancer cells with KRAS mutations are homogeneous because they have the same KRAS mutation., 2 novel mutations (K5E, G12S) were identified in 7 patients withcardio-facio-cutaneous syndrome, Costello syndrome or Noonan syndrome., Report genetic alterations of K-ras in Korean colorectal cancer patients., tumor budding and podia formation were observed to be significantly higher in the 32 (34.7%) of colorectal tumors with K-ras gene mutations (29 mutations in codon 12, 3 in codon 13), data support the notion that K-ras-dependent inhibition of anoikis plays an important casual role in colorectal carcinoma progression, KRAS is rarely mutated in pilocytic astrocytomas., The K-RAS gene was screened for mutations in Congenital cystic airway malformation/congenital pulmonary airway malformation...no mutations were present, Wild type K-ras2 is related to the negative regulation of cell proliferation, metabolism and transcriptional control in colon carcinoma cells., experiments provide a rationale for targeting Ras and associated signaling pathways in mesothelioma and also suggest cap-dependent translation as one mechanism by which Ras induces proliferation in this disease., The regulation of p21WAF1/CIP1, independent of p53 or bcl-2 expression, appears to be associated with Kras mutations., Data suggest that the intrinsic k-Ras/Ras GTPase activity, the responsiveness of these proteins to GTPase-activating proteins, and guanine nucleotide dissociation all regulate developmental programs in vivo., Frequently mutated in high hyperdiploid childhood acute lymphoblastic leukemia., study of point mutations in RAS oncogenes in papillary thyroid carcinoma; 2 mutations found (GAA/CAA at codon 31 of K-RAS & CAA/CAC at codon 61 of N-RAS); data confirm previous studies, showing RAS mutations are more rare in PTC than follicular neoplasms, 54% of childhood CBF-AML had RTKs and/or Ras mutations, In conclusion, the data support a model whereby RbAp48 regulates cellular morphology and cytoskeletal organization by increasing K-Ras activity and signaling through MAPK., KRAS WT status is associated to survival benefit in cetuximab treated metastatic colorectal cancer., k-ras codon 12 mutation is associated with non-small cell lung carcinoma, Smoking and diabetes were associated with pancreatic cancer patients positive for K-ras codon 12 mutations, Quantification of mutant KRAS2 in pancreatic juice differentiates pancreatic adenocarcinoma from chronic pancreatitis, and may be a useful early detection tool for pancreatic cancer., KRAS2 c.34G > T somatic prescreening, followed by MUTYH hotspot mutation analysis when positive, can identify patients with (atypical) MUTYH-associated polyposis, A worse clinical outcome was found for CIMP-high, microsatellite stable colorectal cancer with KRAS/BRAF mutation but not for those lacking KRAS/BRAF mutation., results confirm the high prognostic value of KRAS mutations on response to cetuximab and survival in metastatic colorectal cancer patients treated with cetuximab, All cases were wild-type for HER2. Mutations of EGFR and K-ras genes represent an early event in lung adenocarcinomagenesis, and AAH convincingly seems to be a precursor lesion in a subset of cases of adenocarcinoma., genetic alterations of KRAS and PIK3CA may play equivalent roles in endometrial carcinogenesis, Mutations in the K-ras is associated with colon cancers, The data support that the frequencies and patterns of somatic mutation of the K-ras gene in colorectal cancer are variable among populations., while activated HrasV12 promotes differentiation and growth arrest in these endodermal progenitors, KrasV12 promotes their proliferation, K-ras mutations have a limited role in development of sinonasal cancer, KRAS polymorphisms were indicated to be involved in risk for the development of atypical adenomatous hyperplasia that progresses to lung adenocarcinoma., first direct comparison of survival of resected patients with either EGFR or KRAS mutant lung adenocarcinomas compared with those wild type for both genes; EGFR & KRAS mutations define distinct molecular subsets of resected lung adenocarcinoma, KRAS status should be considered in selecting patients with mCRC as candidates for panitumumab monotherapy, In patients with lung adenocarcinoma, mutation analyses of EGFR and KRAS show whether or not to apply treatments targeting against EGFR and the selection of dosage for such treatments., Our data provide evidence that PIK3CA and BRAF contribute to the tumorigenesis of IPMN/IPMC, but at a lower frequency than KRAS., high frequency of mutations in the PIK3CA, HRAS and KRAS genes leads us to believe that dysregulation of the phosphatidylinositol 3-kinase or Ras pathway is significant for the development and progression of penile carcinoma., apart from K-ras codons 12/13 point mutations, overexpression of the ras family genes is important in the development of colorectal cancer but it appears not to be predictive of survival., The incidence of K-ras mutation may be associated with the hypersecretion of mucin in IPMN patients., KRAS mutation may occur at a very low frequency in Chinese NSCLC patients regardless of pathology, smoking status, or gender., Kras may uniquely contribute to the initiation of tumors in endodermally-derived tissues by expanding a stem/progenitor cell population, Data show that germ cell single base substitution mutation frequencies are very similar to somatic tissue Kirsten-RAS mutation frequencies., Before panitumumad administration KRAS oncogene must be analysed to determine "continuous activation" or wild type gene is involved., K-ras mutation has been detected in the tumor tissue of 25 patients (33%). K-ras mutation hasn't been detected in the blood. tumors with K-ras mutation have a worse prognosis and often lead to disemination, CpG island methylator phenotype in colorectal neoplasms may result from activating mutations in either BRAF or KRAS., The G-rich strand of a nuclease hypersensitive element, located in the human KRAS promoter, can fold into a dynamic intra-molecular G-quadruplex that can assume two distinct conformations., may be involved with imatinib resistance in chronic myeloid leukemia, Provide a unique view of the tumor-initiating effects of oncogenic KRAS in a zebrafish model of pancreatic cancer., Increased frequency of K-ras mutations are associated with colorectal oncogenesis, KRAS mutations are associated with cetuximab failure in EGFR FISH+ colorectal cancer., RAS signaling network is extensively dysregulated in colorectal carcinomas., Mutational activation of the K-ras gene, HPV infection and tobacco or alcohol abuse, can be considered independently or in combination as high risk factors for esophageal squamous cell carcinoma development., A variety of molecular assays have been devised to detect mutated KRAS in pancreatic cancer., analysis of a signaling mechanism for the regulation of the Ras/ERK pathway based on the eNOS-dependent differential activation of N-Ras and K-Ras at specific cell compartments, K-RasG12D-induced T-cell lymphoblastic lymphoma/leukemias harbor Notch1 mutations, This is the first report in colorectal carcinoma of humans of internal tandem duplication longer than 1 codon in th KRAS gene and first insertion detected in exon 2., KRAS mutations and PI3KCA/PTEN deregulation significantly correlate with resistance to cetuximab., both Kras and integrin alpha1beta1 cooperate to drive the growth of non-small cell lung cancer in vivo, All of the KRAS-mutant Microsatellite instability (MSI)-H (high) tumors harbored sequence alterations MLH1, which implies that KRAS mutation more frequently and almost exclusively occurs in DNA mismatch repair gene-mutant MSI-H tumors., Mutation in KRAS is associated with childhood acute lymphoblastic leukemia, KRAS and BRAF mutations can impair response to anti-EGFR therapy for colorectal neoplasms, Bayesian network analysis of these and other datasets revealed that PTRF might be a potentially important component of the ERBB signaling network, BRAF, KRAS and PIK3CA mutations occur prior to malignant transformation demonstrating that these oncogenic alterations are primary genetic events in colorectal carcinogenesis, All K-ras positive patients revealed a poor survival prognosis and had a tumor relapse after resection., With at least 3 markers methylated, new CIMP-positive colorectal cancers were closely associated with proximal tumor location, low frequency of KRAS mutation, and high frequency of BRAF mutation., although the PAK4 gene is not activated by mutation in cell lines with gene amplification, an oncogenic form of the KRAS2 gene is present in these cells and oncogenic KRAS2 can activate PAK4, The LCS6 variant allele in a KRAS miRANA complementary site is significantly associated with increased risk for NSCLC among moderate smokers., The frequency of KRAS mutations in the melanocytic aggregate (five of 18, 28%) was second to BRAF V600E, while in melanoma, the frequency was also second to BRAF V600E, Patients with a colorectal tumor bearing mutated K-ras did not benefit from cetuximab, whereas patients with a tumor bearing wild-type K-ras did benefit from cetuximab., Hereditary pancreatitis patients with PRSS1 mutations also had mutations in BRAF and KRAS2., KRAS mutation is related with a random CpG island methylation pattern which may lead to CpG island methylator phenotype in colorectal cancer ., the presence of mutations in the KRAS oncogene can be used to predict which patients are unlikely to benefit from treatment with epidermal growth factor receptor-directed therapy., ovarian cancer patients with KRAS or BRAF mutations may benefit from CI-1040 treatment, Mutations in the KRAS are associated with Noonan syndrome., The digital melt curve assay detected 16 (59%) of 27 advanced adenoma samples that contained KRAS mutations, compared with 7% with the Hemoccult, 15% with the HemoccultSensa, and 26% with the PreGenPlus assays., KRAS mutations in either primary or metastatic tumors from patients with colorectal cancer is concordant., The prevalence of mutant KRAS2 is similar in familial pancreatic adenocarcinoma as in sporadic pancreatic adenocarcinomas., presence of the KRAS G12V mutation in the cells escaping apoptosis and inducing angiogenesis via IL8 may confer a more aggressive phenotype, KRAS, and CMET mutations are associated with advanced non-small cell lung cancer., KRAS mutations or TP53 mutations are associated with lung adenocarcinoma., to find kRAS mutations in bladder tumor samples, p53 mutation is an initiating mutation in the majority of colitis-associated neoplasia, and K-RAS activation is an alternative gatekeeping mutation., oncogenic KRAS could cause the accumulation of phosphatidylinositides and modulate the cell shape and migration., Evidence from several randomized studies has established that advanced colorectal tumors harboring a mutation in the KRAS gene do not respond to epidermal growth factor receptor-directed monoclonal antibodies, such as cetuximab or panitumumab., miR-143 is significant in suppressing colorectal cancer cell growth through inhibition of KRAS translation., p21(Ras)-mediated survival signaling is regulated by via a PI(3)K-AKT pathway, which is dependent upon both PDK1 and PKCdelta, and PDK1 activates and regulates PKCdelta to determine the fate of cells containing a mutated, activated p21(Ras)., The genes involving MSI-L carcinogenesis are similar to MSS but the timing and frequency of the KRAS mutation is different., mutations are associated with post-operative recurrence of lung adenocarcinomas, KRAS mutations were associated with lower response rate to cetuximab plus irinotecan in colorectal cancer patients(4% v 27% in nonmutated patients; P = .021) and shorter PFS (3.0 v 5.3 months; P = .021)., MGMT hypermethylation is associated with G, activation of PIK3CA may be an important molecular event contributing to the maintenance of OSE transformation initiated by oncogenes such as K-ras, Report the importance of KRAS mutations and EGF61A>G polymorphism to the effect of cetuximab and irinotecan in metastatic colorectal cancer., Mutation in KRAS is associated with adrenocortical carcinomas., Distinct BRAF (V600E) and KRAS mutations in high microsatellite instability sporadic colorectal cancer in African Americans., Overexpression and mutations of Kras lead to common altered gene expression patterns in NIH3T3 cell., KRAS2 mutations in human pancreatic acinar-ductal metaplastic lesions are limited to those with pancreatic intraepithelial neoplasia., mutation in KRAS were associated with increased resistance to gefitinib in lung cancer cell lines, Mutations of KRAS were present in 9.6% (9 of 94) of the samples, We found KRAS2 gene mutations at codon 12 in all eight cases of Adenosquamous carcinoma of the pancreas, There was no significant predictive value for therapeutic response of K-ras mutations for advanced non-small cell lung cancer., study of KRAS/BRAF mutation status in a large and well-documented cohort of primary and metastatic renal cell carcinoma, hnRNP A1/Up1 completely abrogates the cooperative quadruplex-to-ssDNA transition that characterizes the KRAS quadruplex and facilitates the association between the quadruplex and its complementary polypyrimidine strand., k-ras mutations are associated with advanced pancreatic carcinoma in response to combined gefitinib, paclitaxel, and 3-dimensional conformal radiation treatment., The benefit of cetuximab was limited to patients with KRAS wild-type tumors., quercetin and luteolin significantly decreased ERK phosphorylation, In this review, we summarize the initial discovery of RAS mutations in NSCLC, describe work exploring associations with clinical factors and outcomes, and provide an overview of current approaches to targeting KRAS mutant NSCLC., KRAS mutations were found in 60 (15%) samples with 58 ovarian samples deriving from malignant tissue and 2 samples deriving from benign tissue., miR-18a* may function as a tumor suppressor by targeting on K-Ras. Therefore, the miRNA may also be a potential therapeutic agent or target for cancer therapy., EGFR/KRAS mutation testing of multiple lung adenocarcinomas can assist in differentiating multiple primary lung adenocarcinomas from metastatic lesions., Several key studies have demonstrated that patients with mutant KRAS do not respond to treatment with epidermal growth factor inhibitors. This finding has several implications for clinicians who treat patients with metastatic colorectal cancer., cases with the KRAS-LCS6 variant have significantly reduced survival time and suggest that this variant may alter the phenotype or therapeutic response of this disease., EGFR-targeting monoclonal antibodies such as cetuximab or panitumumab are ineffective in patients with activating mutations in KRAS.[review], study reports on the occurrence of premature closure of cranial sutures in subjects with Noonan syndrome, and their specific association with mutations in the KRAS gene, KRAS mutational analyses could help to identify a subgroup of patients with metastatic colorectal neoplasms who have higher chances of benefiting from EGFR inhibition., Codons 12 & 13 of K-ras were mutated in 23.33% of patients. 28.57% were at codon 12, 57.14% were at codon 13, & 14.29% at both. They were more frequent in tumors in the left hemicolon and in well-differentiated adenocarcinomas & mucinous carcinomas., KRAS mutation is a relatively common event in endometrial carcinogenesis, but with no prognostic value., Mutations in KRAS were found in 30% patients in the low-grade carcinoma group, however, they were not found in the high-grade carcinoma group. KRAS and BRAF mutations were mutually exclusive, and both mutations were observed in 40%., oncogenic properties of KRAS and BRAF but not NRAS, HRAS, and PIK3CA contribute to the tumorigenesis of periampullary and ampullary tumors, Data show that KRAS mutation was detected in 201 tumours (39.4%)., data confirm that KRAS and BRAF mutations do occur in the same cell and that BRAF V600E mutation is associated with CIMP+ status., These findings point to a previously underappreciated role of Ras in mitotic progression and demonstrate that mitotic stress induced by the Ras oncogene., KRAS mutations are associated with colorectal neoplasms., Alterations in TP53, APC, K-ras, and DCC genes in the non-dysplastic ulcerative colitis and Crohn's disease colon, were analyzed., overexpressed wild-type KRAS has a role in downstream signaling and cancer cell growth, Review, Detection of KRAS mutational status in CTCs, by gene expression array, has potential for clinical application in selecting metastatic colorectal cancer patients most likely to benefit from cetuximab therapy., Ki-ras mutations (Table 3) showed that rectal tumors were more likely to have mutations in Codons 12 and 13 than either proximal or distal colon tumors, Mutation pattern of K-ras gene is associated with colorectal cancer., Data demonstrate that the hypervariable region of K-Ras4B contributes in a major way to the interaction with calmodulin, while the catalytic domain of K-Ras4B provides a way to control the interaction by nucleotide binding., Results suggest that the mutations of EGFR, KRAS, BRAF between primary tumors and corresponding lymph node metastases should be considered whenever mutations are used for the selection of patients for EGFR-directed tyrosine kinase inhibitor therapy., Assessing KRAS and BRAF mutations might help optimising the selection of the candidate metastatic colorectal cancer patients to receive anti-EGFR moAbs., KRAS mutation was associated with lack of response (P=0.002) and shorter progress free survival (P=0.09) in patients with metastatic colorectal cancer., Data show that the presence of a K-ras mutation (13.3%) was not associated with either PFS or OS., strong inter-relation between DR4 AND DR5 overexpression and presence of oncogenic KRAS/ BRAF mutations in colon cancer., KRAS mutation may only be involved in carcinogenesis of partial gastric cancers and the different mutation types of KRAS may take part in development of gastric cancer at different stages., existing evidence on the relationship between K-ras mutations and tobacco smoking in adenocarcinomas of the pancreas, colorectum and lung [review], study of colorectal cancer cell lines that differed only in the mutational status of their KRAS or BRAF genes; data suggest that glucose deprivation can drive acquisition of KRAS pathway mutations in tumors, No difference in outcome was seen between patients harboring KRAS transition versus transversion mutations in non-small cell lung cancer., High-throughput copy number and gene expression data of 36 microsatellite stable sporadic colon cancers resected from patients of a single institution characterized for mutations in APC, KRAS, TP53 and loss of 18q were analyzed., KRAS mutations correlate with expression of DCN and TPM1 in colorectal cancer., Mutations in KRAS protein is associated with Colorectal Carcinoma., In colorectal neoplasms a mutation frequency of 40% and a cluster of three mutation types (p.G12D, pG12V, and p.G13D) in primaries and metastases can be defined as benchmarks for routine KRAS analyses., Investigated the prevalence of PTPN11, HRAS, KRAS, NRAS, BRAF, MEK1, and MEK2 mutations in a relatively large cohort of primary embryonal Rhabdomyosarcoma (RMS) tumors. HRAS and KRAS were found to be rarely mutated., KRAS mutation is associated with sarcomatoid carcinomas of the lung., Several studies have demonstrated the absence of objective response in patients treated with irinotecan-cetuximab after failure of irinotecan, when the tumour presents a KRAS mutation., K-RAS mutations were more frequent in males and were associated with smoking habits in 411 lung adenocarcinomas, In all cases of our series of patients with squamous cell anal carcinoma wild-type K-ras was observed., KRAS mutation correlates with accelerated metastatic progression in patients with colorectal liver metastases., EGFR and KRAS status of primary lung carcinomas may not predict the status in the corresponding metastases., LIN28B plays an important role in radiation responses of lung cancer cells through inhibiting let-7g microRNA processing and increasing translation of KRAS., a sizable subgroup of non-small cell lung carcinomas harbor KRAS amplification, some of which also contain point mutations, and suggest that an increased KRAS copy number may drive p21 overexpression., KRAS mutations are associated with non-small cell lung cancers., KRAS mutations affect tumor necrosis factor-induced apoptosis in colon carcinoma cells via ERK-modulatory negative and positive feedback circuits along with non-ERK pathway effects., organochlorine compounds and coffee may have independent roles in the aetiopathogenesis of pancreatic ductal adenocarcinoma through modulation of KRAS activation, Studies provide models for Ras in association with Raf kinase, RalGDS and PI3Kalpha and PI3Kgamma., KRAS mutation and microsatellite instability are associated with colorectal cancer., incidence of KRAS mutation; KRAS splice variants, RAS and CSF3R mutations in severe congenital neutropenia., Oncogenic KRAS and BRAF differentially regulate hypoxia-inducible factor-1alpha and -2alpha in colon cancer , and this may potentially contribute to the phenotypic differences of KRAS and BRAF mutations in colon tumors., Suppression of TBK1 induced apoptosis specifically in human cancer cell lines that depend on oncogenic KRAS expression, EGFR and KRAS mutations were found in 33 (10%) and 78 (23%) of lung adenocarcinomas, respectively, whereas 226 (67%) cases were negative for both mutations, assessment of KRAS mutations in juvenile myelomonocytic leukaemia, Data show that NF-kappaB functions downstream of Ras to promote epigenetic downregulation of FBP1., BRAF and KRAS oncogenes have different transforming capability in colon cancer, KRAS and BRAF mutations in advanced colorectal cancer are associated with poor prognosis but do not preclude benefit from oxaliplatin or irinotecan., BRAF status, EGFR amplification, and cytoplasmic expression of PTEN were associated with outcome measures in KRAS wild-type patients treated with a cetuximab-based regimen., analysis of KRAS mutation in tumor samples by PCR and sequence analysis, Study identified the previously reported pathogenic mutation of NTRK3 in a KRAS/BRAF wild-type tumor and 2 somatic mutations in the Src family of kinases (YES1 and LYN) that would be expected to cause structural changes., The high number of KRAS mutations in codons 61 and 146 emphasizes the importance to expand current mutation analyses, Mutation in KRAS reduces the effectiveness of Cetuximab combined with chemotherapy in advanced colorectal cancer patients., VEGFR1, VEGFR2, and PDGFRalpha are over-expressed in K-ras mutated colorectal adenocarcinoma., KRAS mutation is associated with resistance to EGFR-I therapy in colon cancer., frequency of KRAS and p53-Ab correlates with tumor stage only in the Type I endometrial carcinoma, In this study the presence of mutations at codon 12 of the KRAS gene in 78 women with ovarian tumor were studied to see if there was a link., The study suggests that activating KRAS mutants is a particularly important independent predictive marker in metastatic colorectal cancer patients treated with cetuximab, Screening for BRAF, RET, KRAS, NRAS, and HRAS mutations, as well as RET-PTC1 and RET-PTC3 rearrangements, was performed on cases of Hashimoto thyroiditis with a dominant nodule, These results suggest a role for KRAS mutations in the propensity of primary colorectal tumors to metastasize to the lung., Molecular studies showed 3 (20%) of 15 oncocytic adenocarcinomas of lung with EGFR mutations and 3 additional cases with KRAS mutations., Matrix-assisted laser desorption ionization remains a potent and highly clinically significant predictor of survival after first-line treatment with erlotinib in non-smll-cell lung patients with wild-type EGFR and independent of mutations in KRAS., KRAS mutations only in metastases is not associated with resistance to anti-EGFR treatment in primary colorectal tumors., 18/19 (94.7%) metastatic colorectal cancer smears were perfectly adequate for codon 12 and 13 KRAS mutational analysis by direct gene sequencing., developed two multiplex assays that simultaneously screen 22 nucleotides in the KRAS, NRAS, BRAF and PIK3CA genes for mutations. The assays were validated on 294 tumor DNA samples from patients with advanced colorectal cancer, KRAS mutation testing, preferably at diagnosis, must now be considered a new standard of care for patients with metastatic colorectal cancer being considered for EGFR-targeting, Tumors from A/J and cBy mice displayed different Kras mutations that were remarkably similar to the variations in mutation spectrum reported in smokers and never smokers., KRAS mutations were solely and significantly linked to ERK activation in lung adenocarcinoma., phosphoinositide 3-kinase and RAS-RAF pathways drive the activity of RAF265, a novel RAF/VEGFR2 inhibitor, and RAD001 (Everolimus) in combination, Mutations in TP53, KRAS, or EGFR are not major contributors to the RCC development even in the absence of VHL inactivation., whereas H-Ras and N-Ras were unable to localize to the plasma membrane in the presence of USP17, K-Ras4b localization was unaffected, Mutations in KRAS is associated with lung adenocarcinoma., Specific KRAS mutation is an informative prognostic factor in both sporadic and hereditary CRC and applied in an algorithm with BRAF(V600E) and MSI may identify sporadic CRC patients with poor clinical outcome., data support the model of BRAF and K-ras mutations arising in distinct colorectal cancer subsets associated with different clinicopathological and dietary factors, acting as mutually exclusive mechanisms of activation of the same signalling pathway, KRAS mutations are associated with relapsed childhood high hyperdiploid acute lymphoblastic leukemia., Our study suggests that mutations of KRAS, not BRAF, may play a role in the pathogenesis of prostate carcinoma in Chinese patients., KRAS mutations in traditional serrated adenomas from Korea herald an aggressive phenotype., K-RAS codon 12 GAT mutation is present at measurable levels in normal appearing mucosa. All tumors carried K-RAS mutation, in most cases as a mutant subpopulation., KRAS mutations contribute to evolution of chronic myelomonocytic leukemia to the proliferative variant., analysis of KRAS mutations in Slovene patients with colorectal cancer, Our results showed significant number of EGFR FISH positive/amplified lung adenocarcinomas harboring KRAS mutation, KRAS mutations are very infrequent in triple-negative breast tumors., Suggest that most (but not all) commercial services provide analysis that is accurate and comparable with direct sequencing for KRAS mutations in colorectal neoplasms., K-ras mutations did not have any significant effect on Sorafenib treated patients with advanced non-small cell lung cancer., Only one mutation in the K-RAS gene was identified in tonsil squamous cell carcinoma cohorts., Our study indicates for the first time, that oncogenic ras and loss of Smad signaling cooperate to upregulate EGFR and erbB2, which plays a role in promoting invasion., The formalin-fixed and paraffin-embedded samples from 60 patients with colorectal cancer were tested and 19 mutations were detected in KRAS gene., In line with a redirection of autocrine toward paracrine HH signaling by a KRAS-DYRK1B network, we find high levels of GLI1 expression restricted to the stromal compartment and not to SHH-expressing tumor cells in pancreatic adenocarcinoma., activation of K-ras did not depend upon EGFR and resulted in the phosphorylation of Akt and induction of VEGF expression, Data show that FcgammaRIIa and FcgammaRIIIa polymorphisms are not useful as molecular markers for outcome in mCRC patients, and KRAS status and skin toxicity are the only reliable biomarkers to identify patients that would benefit from anti-EGFR therapy., KRAS mutations are associated with lung adenocarcinomas., KRAS gene mutations are associated with non-small cell lung cancer., HER2, but not EGFR gene amplification, is frequently observed in KRAS and BRAF wild type colorectal cancer patients, Observed a significant association of SMAD4 gene aberrations with KRAS mutant status suggesting the involvement of at least two molecules in the advanced tumor grade in colorectal cancers in a Kashmiri population., biological, biochemical and prognostic significance of Ras pathway alterations in colorectal and other solid tumor malignancies; mutations in exon 4 of KRAS were found to occur commonly and to predict a more favorable clinical outcome in colorectal cancer, PIK3CA mutations may have a role in KRAS and BRAF wild type colorectal cancer, High resolution melting is a reliable screening method to identify mutations in the KRAS gene in colorectal cancer., Only a single gene alteration, of uncertain role, was found in the KRAS gene in an Noonan syndrome patient also presenting a PTPN11 gene mutation., The meta-analysis strongly suggests that KRAS mutations represent adverse predictive and prognostic biomarkers for tumour response and survival in mCRC patients treated with cetuximab., assessment of K-ras gene expression changes in the development of the HPV positive cervical cancers; findings indicate high expression of ras among high risk HPV infection can be a marker of cervical cancer development, Mutations in KRAS and BRAF genes are not directly implicated in the development of a MELF (macrocystic, elongated, and fragmented) pattern of invasion in endometrial carcinoma., analysis of EGFR and KRAS mutations in non-small cell lung cancer (NSCLC) patients treated with tyrosine kinase inhibitors, Results are the first to indicate that the KRAS 3'UTR polymorphism may predict for cetuximab responsiveness in KRASwt mCRC patients., Findings identify miR-96 as a potent regulator of KRAS in pancreatic cancer., Using traditional PCR and direct sequencing, we found KRAS mutations in 47 (40%) patients and BRAF(V600E) in 10 (8.5%), Clinical relevance of KRAS in human cancers., if KRAS is not mutated, assessing BRAF, NRAS, and PIK3CA exon 20 mutations (in that order) gives additional information about the efficacy of cetuximab plus chemotherapy in metastatic colorectal cancer., EML4-ALK fusion gene was present at a high frequency in Chinese NSCLC patients, particularly in those with adenocarcinomas lacking EGFR/KRAS mutations, PCR is practically applicable to KRAS/BRAF genotyping using small amounts of biopsied colorectal tumor cells., Of the 750 cases of rectal cancer with tumor mutation information, 28.9% had a KRAS2 mutation, and 48.3% had a TP53 mutation. The majority of both KRAS2 and TP53 mutations were transitions., Results suggest that RAGE, NOX, and H-Ras/Raf-1 are implicated in the up-regulation of HSF1 or PAI-1 in vascular EC under diabetes-associated metabolic stress., samples of metastatic colorectal cancer were tested for the presence of the seven most common mutations in the KRAS gene and the V600E mutation in the BRAF gene, Findings support the hypothesis that the KRAS-variant is a genetic marker for increased risk of developing OC and suggest that the KRAS-variant may be a new genetic marker of cancer risk for HBOC families without other known genetic abnormalities., data provide evidence that c-Kit, p53 codon 72, and K-ras codon 12 are independent prognostic factors in patients with stage II colorectal cancer, KRAS gene mutations are associated with lung adenocarcinomas with features of the mucinous subtype of bronchioloalveolar carcinoma., Over expression of pro apoptotic markers, frequently downregulated miR-217 can regulate KRAS and function as a tumor suppressor in pancreatic ductal adenocarcinoma (PDAC)., KRAS-variant frequencies might be increased among BRCA1 carriers, The frequency of K-RAS gene mutations with non-small cell lung cancer in our center is very low and is similar to that in Asia patients, and is lower than that in Caucasian population., Investigated the methylation of the SFRP2, P16, DAPK1, HIC1, and MGMT genes, as well as the mutation of amino acid codons 12 and 13 of the KRAS gene in normal and tumor tissue DNA of patients diagnosed with sporadic colorectal cancer., Wild-type K-Ras.GTP in association with Gal-3 contributes to thyroid carcinoma malignancy., K-ras mutation in blood appears to indicate K-ras mutation in tumour, while the absence of blood K-ras mutation does not prove lack of mutation in the tumour., Somatic mutations in K-ras and epigenetic alterations in SFRP2 genes play a role in development of mucinous type anal adenocarcinoma., a natural history for hyperdiploid leukemia in which prenatal mitotic catastrophe is followed by a postnatal KRAS mutation to produce the leukemic cell phenotype., The amplification-refractory mutation system with formalin-fixed, paraffin-embedded specimen-derived DNA samples of the human KRAS protein exhibited an acceptable feasibility and robustness suitable for routine clinical practice., In KRAS mutant tumors, PIK3CA mutation restores cyclin D1 expression and G(1)-S cell cycle progression so that they are no longer dependent on KRAS and MEK/ERK signaling., KRAS mutation is associated with anti-EGFR therapy response in colorectal cancer., presence of activating KRAS mutations is significantly correlated to an upregulation of 13 genes (adjusted P-value <0.05), among them DUSP4, a MAP-kinase phosphatase, and SMYD3, a histone methyltransferase, Noonan syndrome and systemic lupus erythematosus is reported in a patient with a novel KRAS mutation., study supports that mutations in the KRAS gene make at least a minor contribution to OSCC tumorigenesis, Expression level of EGFR protein and mutation frequency of KRAS gene in primary tumors were higher than that in metastases., data show that EGFR gene copy number and KRAS mutation status are neither predictive nor prognostic factors for pathological tumour response and disease-free survival in locally advanced rectal cancer patients treated with preoperative chemoradiation, K-ras exon 1 gene mutations were found with low frequency in the bladder cancer tumors from Kashmir valley, which suggests that K-ras gene might be involved in a sub-set of bladder tumors., review focused on KRAS gene mutations with special reference to lung cancers, and pointed out important issues remaining to be resolved [review], KRAS mutation is associated with lung cancer., Kras gene mutation and copy number is associated with thymic carcinomas and thymomas., Preoperative chemoradiation with cetuximab, irinotecan, and capecitabine was active and well tolerated. KRAS mutation status was not a predictive factor for pathologic response in this study., Report on the clinical utility of reflex testing of resected stage I through III lung adenocarcinomas for EGFR and KRAS mutatations., The presence of KRAS mutations and loss of PTEN expression were not associated with impaired response to cetuximab-based chemoradiotherapy and 3-year disease free survival., role of germline KRAS mutations in developmental disorders, Sixty-nine per cent of endocervical-like mucinous borderline tumour of the ovary showed KRAS mutations, KRASG12D is associated with pancreatic cancer., K-ras mutation targeted to gastric tissue progenitor cells results in chronic inflammation, an altered microenvironment, and progression to intraepithelial neoplasia., The KRAS mutation is a negative predictive factor for survival in patients rectal and colon cancer., Results reveal an unexpected role for WT1 as a key regulator of the genetic network of oncogenic KRAS and provide important insight into the mechanisms that regulate proliferation or senescence in response to oncogenic signals., Genetic alterations of K-ras may reflect prognosis in stage III colon cancer patients below 60 years of age., KRAS mutation-positive lung cancer displaying high levels of Myc could be treated by inhibiting Myc transactivation function., REsults show a high concordance in the KRAS status between the primary tumour and metastases., findings indicate that somatic mutations in KRAS and PIK3CA but not BRAF oncogenes are closely associated with the development of cholangiocarcinoma in Chinese population, Mutation of oncogene K-ras at codon 12 and codon 13 is a common molecular event in colorectal carcinogenesis, which might be related with age and tumor location., We report 2 cases with Autoimmune lymphoproliferative syndrome-like disease with somatic KRAS mutation, KRAS signaling pathway alterations in microsatellite unstable gastrointestinal cancers., Data reveal that HIF-1alpha and HIF-2alpha work together to modulate cancer metabolism and regulate genes signature overlapping with oncogenic KRAS., mutations at codon 12 in plasma DNA is not a prognostic factor in advanced non-small cell lung cancer patients, we demonstrate that somatic mutations in the related KRAS gene can also be associated with a nonmalignant syndrome of autoimmunity and breakdown of leukocyte homeostasis, Multiple cellular proteins control the dynamics of membrane association and intercompartmental movement of K-ras to an important degree even under basal cellular conditions., let-7a over-expression represses the expression of k-Ras protein and significantly inhibits the growth of A549 lung cancer cells., Study suggests that concomitant expression of MMP-7 and IGF type 1 receptor correlates with poor prognosis in WT KRAS patients treated with anti-EGFR., Mutations of EGFR, BRAF, and KRAS in adenocarcinoma were mutually exclusive and inversely correlated with RASSF1A methylation, Data show that among 181 CRC patients, stratified by microsatellite instability status, DNA sequence changes were identified in KRAS (32%), BRAF (16%), PIK3CA (4%), PTEN (14%) and TP53 (51%)., K-ras mutations appear more homogeneously distributed than methylation of p16 and MGMT and LOH at 18q, 17p, and 5q in colorectal cancer, Pyrosequencing provided sufficient analytical sensitivity and specificity to assess the KRAS mutation status in routine formalin-fixed CRC samples., Twenty paired specimens of colorectal cancer and adjacent normal tissues were examined for K-ras mutations and annexin A1 expression., This review focuses on current knowledge regarding the molecular landscape of metastatic colorectal cancer including and beyond KRAS, and will summarize novel rationally-developed combinatorial regimens that are being evaluated in early clinical trials., KRAS gene mutations are widely recognized alterations involved in biology and the clinical management of lung adenocarcinoma.This review reports the molecular bases that have led clinical application of detection for such genetic impairments., KRAS mutations are a predictor of resistance to panitumumab or cetuximab.Studies of patients receiving treatment show that tumors carrying KRAS mutations don't respond to EGFR-targeted monoclonal antibodies or show survival benefit from such treatments., Primary esophageal melanomas of Caucasian patients harbor mutations of c-Kit, KRAS and BRAF in varied frequencies., Kras mutation plus increased copy number is associated with non-small cell lung cancer., Data show that KRAS mutation and PTEN protein expression are significantly correlated with the response rate and survival time of Chinese metastatic colorectal cancer patients treated with cetuximab., KRAS and RREB1 are targets of miR-143/miR-145, revealing a feed-forward mechanism that potentiates Ras signaling, Data suggest that expression status of AR and EPI mRNAs might be evaluated as dynamic predictors of response in KRAS WT patients receiving any cetuximab-based therapy., KRAS mutations arise more frequently than BRAF mutations in Moroccan patients with colorectal carcinomas., Mutations in PIK3CA, KRAS and NRAS were exclusive to tumors of uterine origin and age-adjusted Cox proportional hazards modeling associated advanced age, stage and TP53 mutations with decreased survival in the uterine subset., Mutated KRAS status in tumors of Japanese patients with metastatic colorectal cancer is associated with lack of response to panitumumab therapy, KRAS(G12V) enhances proliferation and initiates myelomonocytic differentiation in human stem/progenitor cells via intrinsic and extrinsic pathways., Combination chemotherapy with biweekly cetuximab and irinotecan was effective for pretreated metastatic colorectal cancer with wild-type KRAS., Hepatocellular carcinoma with persistent hepatitis B virus infection shows unusual downregulation of Ras expression and differential response to Ras mediated signaling., KRAS mutation analysis helps to differentiate between pulmonary metastasis from colon adenocarcinoma in situ and primary lung adenocarcinoma, In a group of clinically selected patients, EGFR and KRAS analysis was able to define distinct molecular subsets of lung adenocarcinoma., 40 KRAS wild-type, 40 codon 12-mutated and 32 codon-13 mutated samples were analysed by Ampli-set-K-RAS and K-RAS StripAssay kit., study analyzed 90 samples of cutaneous T-cell lymphomas patients and found 2 KRAS (G13D) and 2 NRAS (Q61K) mutations, KRAS mutation is associated with treatment response for metastatic colorectal cancer., Compared with wild-type KRAS colorectal cancers, KRAS-mutated CRCs had a lower frequency of high microsatellite instabilities, a higher chance of having brisk mitosis and apoptosis, and a greater mean of mitotic figures and apoptotic cells, KRAS mutation seems to be associated with metastasis in specific sites, lung and brain, in colorectal cancer patients, study demonstrates that chip-based TGCE is capable of rapidly screening low-abundance K-ras mutations with high sensitivity, reproducibility, simplicity, and significant savings of time and sample, Studies identify a novel proapoptotic gene target, CYFIP2, which is downregulated by IMP-1, and mediates the regulation of cell survival and K-Ras expression in colon cancer cells., Findings suggest strategies to target nucleolin as a general approach to inhibiting ErbB- and Ras-driven cancers., Data show distinct significant correlations between TITF-1 protein expression and DNA copy gain with mutations in the lung adenocarcinoma-prevalent EGFR and KRAS oncogenes., the role of Pim-1 in pancreatic ductal adenocarcinoma (PDAC) growth transformation and validate Pim-1 kinase as a potential molecular marker for mutated K-Ras activity., There was an incremental increase in KRAS mutation frequency with increasing villous compartment of colorectal neoplasms., KRAS-mutated non-small cell lung cancer cells are responsive to either co-treatment with erlotinib or gefitinib and histone deacetylase inhibitors or single treatment with lapatinib., mutations confer antineoplastic drug resistance, Alterations of the KRAS gene is associated with myelodysplastic syndromes and acute myeloid leukemia., The diagnostic utility of detecting K-ras mutations for the diagnosis of exocrine pancreatic cancer (EPC) has not been properly studied, autophagy is critically involved in malignant transformation by oncogenic K-Ras and show that reactive oxygen species-mediated JNK activation plays a causal role in autophagy induction through up-regulation of ATG5 and ATG7., 140/513 (27.3%) colorectal tumors wildtype for KRAS codons 12 and 13 harbored a mutation in another of the RAS pathway genes., analysis of gallbladder carcinomas, gallbladder adenomas, and high-grade dysplastic lesions for the BRAF and the KRAS mutations, Activated K-Ras protein accelerates human MLL/AF4-induced leukemo-lymphomogenicity in a transgenic mouse model., K-ras mutations were involved in colorectal laterally-spreading tumors in different manners according to tumor location., Studies indicate that the function of PKCdelta in tumor cells depends on a specific oncogenic context, as loss of PKCdelta in NSCLC cells suppressed transformed growth only in cells dependent on oncogenic K-ras for proliferation and survival., oncogenic Ras efficiently activates the ERK pathway both by activating Raf and by inhibiting MEK SUMOylation, thereby inducing carcinogenesis, Both primary tumours and liver metastases can be used for KRAS mutation analysis., Kras(G12D) allele promotes metastasis in pancreatic cancer cells partly through the downregulation of E-cadherin., A novel polymorphism in codon 25 of the KRAS gene associated with gallbladder carcinoma patients of the eastern part of India, KRAS mutational analysis provides useful additional risk stratification to guide use of adjuvant chemotherapy in colorectal cancer., Effective inhibition of the EGFR signaling by the drug combination in KRAS wild-type cells but not in KRAS mutant cells., data exclude the possibility of an association between KRAS rs61764370 and a clinically significant risk of ovarian cancer or of familial ovarian cancer, Ubiquitination of K-Ras enhances activation and facilitates binding to select downstream effectors., Non-BAC adenocarcinoma is related to smoking history and has a poor prognosis. BAC/adenocarcinoma with bronchioloalveolar features adenocarcinoma, however, has a more favorable prognosis., K-ras gene mutation is a common event in Chinese colorectal cancer (CRC) patients, but may not be a prognostic factor in CRC , while BRAF is rarely mutated in Chinese CRC patients., TF may participate in both K-ras and p53 mutations involved in colorectal carcinogenesis., Allele-specific qPCR assays for the most frequent activating mutations in EGFR, KRAS, BRAF and PIK3CA in tumor-positive fine needle cytological aspirates were compared against histological material of primary tumors., NF-kappaB activation is a novel target of oncogenic KRAS in endometrial carcinogenesis, these results suggest that a considerable proportion of NSCLC in Chinese population showed discrepancy in KRAS and EGFR mutation status between primary tumors and corresponding metastases., Folding motifs have been uncovered in a nuclease hypersensitive element (NHE) with a complex guanine pattern, located in the human KRAS promoter. A new G-rich motif of 21 nt capable of forming a parallel G-quadruplex was disrupted by bound protein UP1., data indicated that colorectal cancers with KRAS and PIK3CA bi-mutations are more likely to develop into liver metastasis, The frequency of KRAS mutations was significantly higher in lesions with the adenomatous pattern than in lesions with the hyperplastic pattern., The KRAS variant might be a genetic marker for development of triple-negative breast cancer in premenopausal women., evaluation of the status of 90 non-selected colorectal cancer Peruvian patients; only 16.7% (15/90) of tumours exhibited KRAS mutations (codons 12 and 13), demonstrate that mutant K-Ras enhances ETS2 loading onto the promoter, and ETS requires its transcriptional activity to increase GSK-3beta gene transcription in pancreatic cancer cells, a possible etiological role of the Ki-ras mutation in the development of the low-grade mucinous tumors of the appendix, Amplification of the driving oncogene, KRAS or BRAF, underpins acquired resistance to MEK1/2 inhibitors in colorectal cancer cells., Frequent mutations of KRAS in addition to BRAF in colorectal serrated adenocarcinoma, Expression of chemokine receptor CCR5 correlates with the presence of hepatic molecular metastases in K-ras positive colorectal cancer., gene amplification is associated with non-small cell lung carcinoma progression in both Swiss and Amertican cohorts, A review of several studies revealed a high rate of compliance of the KRAS gene mutational status in primary and metastatic tumors., Heterogeneity of KRAS and BRAF mutation status intra-tumorally in colorectal cancer was assessed., KRAS mutation in metastatic tumors is more commonly associated with advanced stages of cancer and correlates with a heavy smoking history., KRAS mutations in 23 adenosquamous carcinomas of lung, Combined KRAS and TP53 mutation status is not predictive in CAPOX-treated metastatic colorectal cancer., Semiquantitative analysis of K-ras point mutation in endoscopically-collected pancreatic juice appears to be a useful tool for identifying chronic pancreatitis patients at high risk for developing pancreatic cancer., c-Raf plays a unique role in mediating K-Ras signaling in non-small cell lung carcinoma and makes it a suitable target for therapeutic intervention., K-ras gene mutations were detected in four NSCLC cases (3.5%)., Using human CRC samples, authors were able to show that there is crosstalk between the KRAS-mediated pathway and other signalling pathways., the KRAS-variant was enriched in non-acral melanoma (25%), and miR-137 under expression was significantly associated with melanomas with the KRAS-variant., Data show that IL-8 overexpression is induced by activating mutations of KRAS or EGFR in non-small cell lung cancer (NSCLC) cells., KRAS mutation status is a treatment effect modifier for anti-EGFR antibodies in metastatic colorectal cancer, Case Report, K-rasVal12 and mutant Apc have a synergistic role in intestinal neoplasms, Heterogeneous distribution of K-ras codon 12 and 13 mutations within primary tumor, or between primary tumor and lymph node metastases, was demonstrated for 15 (20%) of 74 colon cancer patients having K-ras mutations., To define functions of STAT3 in vivo, authors test the impact of conditional inactivation of STAT3 in KRAS-driven PDAC., the incidence of EGFR and KRAS mutations in Chinese patients with adenosquamous carcinoma of the lung were similar to those of Asian patients with adenocarcinoma, These findings add information about the impact of specific amino acid changes in the Kras gene., low- and high-resolution mapping of nucleosome boundaries around p53 REs within the p21 promoter have provided insight into the mechanism of p53 binding to its sites in cells and the consequent changes in nucleosome occupancy at such sites, Combined mutations in codons 12 and 13 of KRAS are relatively infrequent and most commonly occur in prostate carcinomas., In patients with surgically resected lung adenocarcinomas, the KRAS and EGFR gene mutation status of tumors was not associated with disease-free survival., The incidence of KRAS mutations in Chinese patients with Esophageal Squamous Cell Carcinoma was not low. KRAS mutations were mainly located in codon 12., Stromal cells in colorectal carcinoma do not share KRAS mutations that the epithelial component harbors., The application of highly sensitive methods for the detection of KRAS mutations significantly improves the identification of mCRC patients resistant to anti-EGFR MoAbs., KRAS mutations are not associated with response to Bexarotene plus erlotinib therapy in lung carcinogenesis., the relationship between the mutation of K-ras gene and non-small cell lung cancer, Grossly polypoid colorectal adenocarcinomas with a persistent pre-existing adenomatous polyp with villous architecture are strongly associated with KRAS mutations., A pathway in which Max & RXRalpha inhibit miR-193a activates the PLAU & K-Ras oncogenes is important for distinct aspects of cellular transformation. miR-193a controls anchorage-independent growth in soft agar through K-Ras., mutation kit analysis identified a total rate of 44.8% mutations in patients with colorectal cancer; most mutations (82.4%) were identified within codon 12 and the minority on codon 13, An evaluation of cytomorphologic features of advanced lung adenocarcinomas that might be associated with KRAS mutational status., These data demonstrate a role for rs712 polymorphism of the KRAS in susceptibility of oral squamous cell carcinoma., conclude that, in the colon and pancreas, Cten is a downstream target of Kras and may be a mechanism through which Kras regulates of cell motility, Comparison of KRAS mutation tests in colorectal cancer patients., Mutant KRAS promotes hyperplasia and alters differentiation in the colon epithelium but does not expand the presumptive stem cell pool., In total, 29% of the false-negative or doubtful cytology results were accompanied by RASSF1A methylation or KRAS mutation results that were highly suggestive of malignancy., Combining routine cytology with FISH and K-ras mutational analyses improves diagnostic yield of endoscopic ultrasound-guided fine needle aspiration of solid pancreatic masses., KRAS mutation is associated with nonsmall cell lung cancer., KRAS mutation strongly predicts for a lack of clinically meaningful benefit in colorectal cancer patients., mitochondrial functional loss may be mediated by oncogenic K-Ras-induced mitophagy during early tumorigenesis even in the absence of hypoxia, STK33 downregulation or dominant mutant overexpression had no effect on KRAS signaling or survival of cancer cells., The detection of KRAS mutant allele-specific imbalance in lung adenocarcinomas may identify patients with more aggressive disease., compared with KRAS codon 12 mutations, codon 13-mutated metastatic colorectal cancer presents as a more aggressive disease frequently associated with local and distant metastases at first diagnosis, An unusual phenotypic effect of the specific KRAS mutation or a coincidence of two independent disorders may be considered. KRAS mutation-associated phenotypes appear to be subject to considerable clinical heterogeneity, Data suggest that recurring DNA copy alterations are important for tumor progression in the Kras(LA2) model of lung cancer and that the requirement for these alterations may be dependent on the genetic background of the mouse strain., The KRAS mutation occurred more frequently in lung tumor patients whose ;ung tumor diameter was >/= 31 mm than in those whose tumor diameter was <30 mm., Heterogeneous KRAS mutations within the primary colorectal tumor might play an important role for discordant KRAS status between primary and metastatic sites., Neoadjuvant chemoradiotherapy did not alter KRAS codon 12 or 13 or microsatellite instability results in rectal adenocarcinoma., KRAS mutation is an early hit in lung adenocarcinoma development., Our results suggest that response to Panitumumab treatment is not only controlled by the KRAS status but may also be essentially influenced by other regulating factors., KRAS mutations are associated with treatment response in non-small cell lung cancer., KRAS mutation status predicts a patient's likely response to the monoclonal antibody cetuximab., Mutant KRAS is associated with low drug response in metastatic colorectal cancer., the results provide strong evidence that CTNNB1 is the driver in these contexts and that KRAS(G12D) and Pten loss promote the program set in motion by the CTNNB1., Patients with pancreatic cancer with KRAS mutations showed a worse response to chemotherapy than those with wild-type KRAS., APC and KRAS mutations in distal colorectal polyps are related to smoking habits in men., Genetic analysis revealed individual heterozygous mutations in the KRAS (phenotype of CFC/Noonan syndrome) and BRAF genes (phenotype of CFC syndrome), HKe3 cells stably overexpressing oncogenic KRAS showed increased expression of miR-200c, miR-221 and miR-222 and reduced expression of its target PTEN exclusively in 3D culture. These miRNAs were also overexpressed in colorectal tumor specimens., Under serum-starved conditions, the expression level of RRM2 protein increased in HCT116 cells compared to HKe3 cells (HCT116 cells with a disruption in oncogenic KRAS), and the re-expression of KRAS in HKe3 cells induced the expression of RRM2., The K-RAS protein is associated with mitochondria, and induces a rapid suppression of respiratory chain complex-I and a decrease in mitochondrial transmembrane potential by affecting the cyclosporin-sensitive permeability transition pore., Our method for the detection of KRAS gene mutations may be useful to supplement histo/cytopathologic evaluations for pancreatic cancer, and is superior to serum CA19-9 in EUS-FNAB histo/cytopathology-indeterminate patients, colorectal cancer patients with low levels of tumor-infiltrating lymphocytes , a high CD1a(+)/DC-LAMP(+) tumor-infiltrating DC ratio, and a KRAS mutation in codon 13 are at a high risk of disease recurrences, KRAS mutation is associated with metastatic pancreatic ductal adenocarcinoma., IFN-beta contributes to Ras transformation, Paxillin enables attachment-independent tyrosine phosphorylation of focal adhesion kinase and transformation by RAS, In sporadic colorectal tumourspatients, the most frequently mutated gene was APC (68.9% of tumours), followed by KRAS (31.1%), TP53 (27.2%), BRAF (8.7%) and CTNNB1 (1.9%)., Phospho-ERK and AKT status, but not KRAS mutation status, are associated with outcomes in rectal cancer treated with chemoradiotherapy, KRAS mutation G12V enhances the ability of colon adenocarcinoma cells to migrate and invade through filopodia formation and PI3K-dependent Cdc42 activation, Validated liquid-based cytology for EGFR and KRAS gene mutations and set appropriate laser capture microdissection and direct sequencing benchmarks., KRAS mutation detection may be reliably performed with high accuracy, allowing treatment decisions for lung cancer., KRAS mutations are associated with non-small cell lung cancer., KRAS mutation is associated with metastatic colorectal cancer, KRAS gene may be instable during the metastatic process observed in non-small cell lung cancer, whereas the mutant KRAS genotype in the primary tumor could be more likely to change back to the wild-type after metastasis., KRAS knockdown using shRNA suppressed ERK signaling in all of the KRAS mutant colorectal cancer cell lines examined., Data show that high-resolution melting analysis is a sensitive and accurate screening methodology for K-ras codons 12 and 13 mutations in clinical samples., Results indicate that early-stage colorectal cancer (CRC) with the KRAS-lethal-7 (let-7) miRNA complementary site (LCS6) variant have a better outcome., KRAS mutation is associated with metastatic colorectal cancer., DNA methylation of each marker was quantified using combined bisulfite restriction analysis (COBRA) and analyzed along with various genetic factors associated with CRC [the BRAF and KRAS mutations, MLH1 methylation and microsatellite instability, KRAS mutations in primary NSCLC foci may be a more accurate biomarker than in metastases to reflect KRAS mutation status., strong positive correlation between the fraction of mutated KRAS alleles and the fraction of cancer cells in the samples indicate homogeneity of KRAS mutation status in colorectal carcinoma, Cell growth retardation was inhibited upon knockdown of K-Ras and an increase in the level of miR-622 in 16HBE-T cells, role of KRAS mutations in esophageal squamous-cell carcinoma carcinogenesis (Review), This article reviewes the spectrum of KRAS/BRAF genotype and the impact of KRAS/BRAF mutations on the clinicopathological features and prognosis of patients with colorectal cancer. [review], Letter, study presents a novel functional interaction of p16 and K-Ras. Re-expression of the tumor suppressor in pancreatic cancer cells restricted Ras oncoprotein activity, which resulted in loss or reduction of their transforming potential, KRAS mutant cancer cells showed variable response to AZD6244., loss of heterozygosity at Kras can provide cancer cells functional growth advantages and promote metastasis., African Americans with microsatellite stable tumors had a higher proportion of KRAS mutations than Caucasians that were isolated to proximal colon cancers and primarily driven by mutations in codon 13., Adenoma with intermediate-methylation epigenotype correlated to KRAS-mutation((+))., Data indicate that PIK3CA mutations occur in lung adenocarcinomas, usually concurrently with EGFR, KRAS, and anaplastic lymphoma kinase (ALK)., KRAS mutation is inversely associated with interval cancers and with MSI, suggesting that it is a marker of the chromosomal instability pathway associated with slow tumor growth., Data indicate that RNA interference of KRAS variant caused a significant decrease in cell survival in the KRAS variant carrying epithelial ovarian cancer cell line., This is the first description of an oncogenic gene fusion of KRAS, one of the most studied proto-oncogenes., BRAF and KRAS mutations were observed in six (46.2%) and four (30.3%) filiform serrated adenomaS, respectively., Report validity EGFR and KRAS mutation analysis in cytologic samples of lung adenocarcinoma enabled by laser capture microdissection., A considerable proportion of NSCLC in Chinese patients showed discrepancy in KRAS and EGFR mutation status between primary tumors and corresponding metastases., Report mutations in KRAS, EGFR, and BRAF in cholangiocarcinoma and identify therapeutic targets for tyrosine kinase inhibitors., Mutations in kras proteins are present in benign lichenoid keratosis., This study provides a step forward towards understanding the molecular and pathological significance of the KRAS-variant., Gene mutations of K-ras are not associated with the postoperative prognosis of patients with hepatocellular carcinoma., The small number of tumors with co-expression of mutant K-Ras and MST2 has elevated apoptosis rates, Mutations detected in KRAS in microdissected samples from different areas of the same tumor (colon cancer) differed according to immunophenotype., RET mutations may have a role in medullary thyroid carcinoma, while BRAF, AKT1, and CTNNB1 do not; the role of HRAS, KRAS, and NRAS mutations are not determined, GLUT1 overexpression status was significantly correlated with gene mutation status, including EGFR and Kras, the activity of myeloblastin was significantly altered in the lung adenocarcinoma biopsies harboring a KRAS gene mutation., The significance of tests for KRAS mutation in colorectal cancer is described together with varius test methods for the said mutation.[review], These results strongly suggested that the oncogenic RAS upregulates EZH2 through MEK-ERK signaling, resulted in downregulation of tumor suppressors including RUNX3 in pancreatic carcinogenesis., Plasma cell-free DNA and plasma mutant KRAS levels (pmKRAS) were strongly correlated., Our findings suggest that EGFR/KRAS mutations do not occur in pure pulmonary squamous cell carcinoma (SQCC)., The mutation status of the KRAS gene is likely involved in mTOR pathway and to be a prognosis marker for colorectal cancer in kidney transplantation., Not all mutant KRas proteins affect patient survival or downstream signaling in a similar way. The heterogeneous behavior of mutant KRas proteins implies that ther interventions may need to take into account the specific mutant KRas expressed by the tumor, Savings of drug costs minus the costs for the determination of KRAS status accounted for EUR 779.42 (SD +/-336.28) per patient per cycle., there is a high frequency of G to A transition of codon 12 mutation of the K-ras gene, with significant correlation with tumour size and tumour location, The KRAS status varied among different areas of the same metastatic focus in metastatic colorectal adenocarcinomas., The rareness of the TP53 mutation shown in this study supports that SCC seems to develop from multipotential stem cells in dysplasia or adenocarcinoma. The mutual wild type status of KRAS among the lesions further supported their identical clonality., Mutated Kras(G12D)-activated AP-1 induces IL-1alpha, which, in turn, activates NF-kappaB and its target genes IL-1alpha and p62, to initiate IL-1alpha/p62 feedforward loops for inducing and sustaining NF-kappaB activity., mutations are good markers of different aetiologies and histopathological forms of lung cancers but have little prognostic value, with the exception of KRAS mutation, which may have a prognostic value in ADC., K-RAS mutation may regulate the ERK pathway, which in turn increases the expression of GGT2, These data suggest the activation of mitogen-activated protein kinase pathway as a possible novel mechanism of primary resistance to imatinib in GISTs, KRAS mutation is associated with colorectal serrated adenocarcinoma., KRAS mutant allele-specific imbalance is associated with colorectal adenocarcinoma., findings implicate that N116S change in KRAS is a hyperactive mutation which is a causative agent of Noonan syndrome through maldevelopment of the heart, These findings support the hypothesis that endometriosis-associated and independent endometrioid adenocarcinoma may develop via different molecular pathways and that KRAS mutations have an important role only in the former tumors., An inherited polymorphism of a let-7 miRNA binding site in KRAS leads to abnormal endometrial growth and endometriosis., Colon adenocarcinomas with KRAS mutations have higher survival rates and morphologic characteristics distinct from those with BRAF mutations., Data indicate that 266 (76.2%) tumors harbored EGFR mutations, 16 (4.6%) HER2 mutations, 15 (4.3%) EML4-ALK fusions, 7 (2.0%) KRAS mutations, and 2 (0.6%) BRAF mutations., Report of oncogenic BRAF/KRAS mutations in sporadic glomus tumors., The presence of both KRAS mutations and the active form of NF-kappaB in CRC tumors indicates poor patient prognosis., BRAF genotype, but not KRAS, was found to be an independent prognostic biomarker., KRAS mutation is associated with colorectal cancer., data suggest that TAK1 functions as a prosurvival mediator in cancer cells displaying hyperactive KRAS-dependent Wnt signaling., K-Ras knockdown abolished the insulin-like growth factor-1 (IGF-1)-induced ERK pathway in the K-Ras mt pancreatic ductal adenocarcinomas cells, All mucinous growths in congenital pulmonary airway malformations were characterized by KRAS missense mutations., cigarette smoking may be a stronger risk factor for KRAS mutation-negative tumors located in the proximal colon, The presence of activating GNAS mutations, in association with KRAS or BRAF mutations, is a characteristic genetic feature of colorectal villous adenoma., Oncogenic KRAS can downregulate Bmp4 through a transcriptional pathway that depends on ERK. These findings point to a unique link between two pathways that are frequently altered in colon cancer., analysis of FGFR2 point mutations in 466 endometrioid endometrial tumors and their relationship with MSI, KRAS, PIK3CA, CTNNB1 mutations, KRAS mutations were present rarely in stidied cohort of samples with breast cancer, mutation of KRAS gene may serve as useful clinical tool for analyzing point mutations in various clinical samples, KRAS mutations were found only in the presence of neoplasia in patients with longstanding ulcerative colitis in India., KRAS mutations to be more frequent than NRAS mutations in pediatric patients with acute myeloid leukemia., we have analyzed the prevalence of somatic mutations in the FGFR3, PIK3CA, AKT1, KRAS, HRAS, and BRAF genes in bladder cancers, Four of the 27 patients were positive for K-ras mutation, KRAS mutations are less common than previous reports and do not correlate with survival in pancreatobiliary neoplasms., Data indicate that TaqMan(R) Mutation Detection assay is an important technology to consider in the field of mutation detection for KRAS, BRAF and EGFR point mutation screening., Investigation the prevalence of mutations in the KRAS gene and its correlation with demographic characteristics, tumor location and stage in 100 colorectal carcinoma patients from India., KRAS mutations were higher in males compared to females and higher in adenocarcinomas compared to other forms of lung cancers, expression of these oncogenes markedly stimulated ERK1/2 activities and morphologically transformed IECs., Our data do not support the hypothesis that the KRAS variant rs61764370 is implicated in the aetiology of sporadic or of familial breast cancer., the expression of EGFR protein by immunohistochemistry and KRAS gene mutation at codons 12 and 13 by using paraffin-embedded and formalin-fixed primary tumor tissues from 205 patients with squamous cell carcinoma of the head and neck, KRAS may have a role in response of metastatic colorectal cancer to cetuximab, KRAS mutations play a limited role in the development of sinonasal cancer., In the KRAS gene, 10 substitutions at codon 12 were observed in lung adenocarcinomas from a Chiba Prefecture, Japan cohort., Metopic suture involvement has not been described before, expanding the main different cranial sutures which can be affected in Noonan syndrome and KRAS gene mutations, Mutation of KRAS is associated with colorectal cancer., Twelve of 94 cases (13%) analyzed for KRAS mutations were found to have a mutation in this study of patients with endometrial cancer., KRAS mutations occurred in conventional adenomas, which were more commonly located in the proximal colon and associated with higher risk for colorectal cancer., Mutations in the KRAS gene are a negative predictive factor for response to cetuximab with very high specificity and low sensitivity, CpG island methylation phenotype based on seven loci, BRAF V600E mutation and KRAS mutation in signet ring cell carcinoma were compared with mucinous and conventional adenocarcinomas, Tumors with KRAS mutations and NF-kappaB activation may be a unique subtype of colorectal cancer, and be more tolerant of chemotherapy and have a poorer prognosis., The aim of the present study was to determine the frequency of EGFR and KRAS mutations in non-small cell lung cancer in the West European Dutch population., AKT1-GLI3-VMP1 pathway mediates KRAS oncogene-induced autophagy in cancer cells., KRAS mutations are associated with response to therapy in colorectal neoplasms., Expression of RBM5 mRNA and protein was negatively correlated with expression of EGFR and KRAS mRNA and protein in NSCLC tissues., Of 26 non-small cell lung cancer cell lines, 14 were KRAS mutant and 12 were wild type; short-term GATA2 knockdown led to specific decreased cell viability and increased apoptosis in KRAS mutant NSCLC cells, comparable to the effect seen with loss of KRAS itself., data indicate that miRNA-143 expression levels serve as an independent prognostic biomarker for CRC in KRAS wild-type patients, MSP58 activates the DNA damage response and p53/p21 signaling pathways., In this work we describe a simple and efficient method for synthesis of milligram quantities of functionally active, fully processed K-Ras4B, and we observe K-Ras4B dimerization in vitro., KRAS, BRAF, and PIK3CA mutations in colorectal cancer have sustained prevalence rate in the Taiwanese population., K-ras mutations were detected in 17 (19.3%) colon cancer samples., In the present study, we did not find any significant correlations between KRAS, BRAF and PIK3CA mutations and the loss of PTEN expression and various clinicopathological features in Chinese patients with colorectal cancer., Chemotherapy effect seems to increase with tumor size. However, this small study could not identify subgroups of patients who did or did not derive significant benefit from adjuvant chemotherapy based on T-size or KRAS status., study examined the mutational spectra of Ras isoforms curated from large-scale tumor profiling and found that each isoform exhibits surprisingly distinctive codon mutation and amino-acid substitution biases, KRAS mutations are associated with advanced colorectal neoplasms., Cancer cells expressing oncogenic KRAS were found to be highly dependent on the transcription factor GATA2 and the DNA replication initiation regulator CDC6., The numbers of primary lesions with wild-type and mutant KRAS codons 12 and 13 were 8 and 13, respectively., Single nucleotide polymorphism in KRAS is associated with synchronous endometrial and ovarian cancer., KRAS mutation status is predictive of cetuximab response in the Japanese metastatic colorectal cancer patients., Oncogenic KRAS regulates 3D-specific miRNAs that are possibly associated with colorectal development in vivo., These findings further validate the importance of the KRAS-variant in breast and ovarian cancer risk, and support the association of this variant as a genetic marker for HBOC families previously considered uninformative., this study is the first to examine the prevalence of EGFR and KRAS mutations in a South American Brazilian population., In 76 patients with colorectal neoplasms, 5 missense mutations were detected in KRAS. 7 patients had multiple mutations, MSH2 and KRAS, APC and KRAS., In patients with KRAS wild-type locally advanced rectal cancer, the addition of cetuximab to the chemoradiation with irinotecan plus capecitabine regimen was not associated with improved clinical outcome compared with chemoradiation without cetuximab, KRAS mutation is not associated with response to therapy in metachronous and synchronous metastatic colorectal adenocarcinoma, KRAS and PIK3CA mutations frequently coexist in patients with colorectal cancer, and are associated with clinical characteristics and outcome., Mosaicism for HRAS c.37G>C and KRAS c.35G>A mutations was found in two individuals with Schimmelpenning syndrome., Data indicate that 14% with pancreatic ductal adenocarcinomas (PDACs) and 7% ampullary adenocarcinomas (A-ACs) had mutations in both KRAS and BRAF., KRAS is a target of miR-30c, and that this miRNA suppresses breast cancer cell growth potentially through inhibition of KRAS signaling., The combined effects of EGFR downregulation, ligand competition, and immune effector function conspire to inhibit tumor growth in xenograft models of cetuximab-resistant BRAF and KRAS mutant cancers., Relationship of activating mutation in K-ras gene with essential clinical characteristics of colorectal tumor disease in different age groups., An acetylation-mimetic mutation in K-RAS4B suppressed guanine nucleotide exchange factor-induced nucleotide exchange and inhibited in vitro transforming activity., Six KRAS mutations were detected by cobas that were not detected by Sanger, and five were confirmed by MPP., Investigated correlation between KRAS mutations and characteristics of non-advanced and advanced colorectal adenomas. KRAS mutations were detected in 31 % of the non-advanced adenomas, in 57.5 % of advanced adenomas and in 62.5 % of early carcinomas., Aim of this study was to characterize further the expression of RUNX3 in lung cancers.Inactivation of RUNX3 was observed in 70% of the adenocarcinoma samples, and this was associated with promoter hypermethylation but not biased to EGFR/KRAS mutations., Cetuximab addition to first line chemotherapy seems to benefit patients with KRAS mutant metastatic colorecttal neoplasms., This study emphasizes the functionality of cancer molecular genetic platforms dedicated to KRAS genotyping, which allow the use of molecular predictive biomarkers by different medical institutions., data showed that there was no significant difference in the mutation frequency of the KRAS gene between primary and distant metastatic colorectal tumors or lymph node metastatic tumors, Digital PCR provides a robust, quantitative measure of the proportion of KRAS mutant alleles in routinely obtained samples, KRAS codon 12 mutations (in particular, c.35G>T), but not codon 13 mutations, are associated with inferior survival in BRAF wild-type colorectal cancer., The most significant discovery of the integrated validation is the down-regulation of FABP5 and PDCD4 in KRAS-activated human tumor bronchial epithelial cells., Authors found that EGFR WT/KRAS mutant advanced non-small cell lung cancer patients are associated with an increased resistance to treatment, specific mutant KRAS may account for differential sensitivity to an EGFR tyrosine kinase inhibitor., Lung cancers with acquired resistance to EGFR inhibitors occasionally harbor BRAF gene mutations but lack mutations in KRAS, NRAS, or MEK1., K-RAS mutations and amino acid substitutions are associated with metastatic colorectal cancer., In CRC patients treated with cetuximab, activating mutation signatures for KRAS (75 genes) were developed., A novel interplay between K-ras and H-ras, with possible implications for colorectal carcinogenesis., KRAS mutation is present in a small subset of primary urinary bladder adenocarcinomas., Data indicate that in KRAS mutated tumours increased miR-200b and decreased miR-143 expression were associated with a good progression-free survival (PFS) upon treatment., K-ras mutation is strongly associated with perineural invasion phenotypically. K-ras mutation is an independent prognostic factor of intrahepatic cholangiocarcinoma after hepatectomy., Review and meta-analysis found that K-ras gene mutations seem not to correlate with the prognosis of patients with colorectal cancer., KRAS mutations predicted shorter survival for patients with advanced lung adenocarcinoma., Standard cytology provides adequate material for the assessment of EGFR and Kras mutational status in non-small cell lung cancer and colorectal cancer patients., Oncogenic K-Ras regulates bioactive sphingolipids in a sphingosine kinase 1-dependent manner, the frequency and spectrum of K-ras mutations among colorectal cancers Iraqi patients, CD151 links alpha(3)beta(1)/alpha(6)beta(1) integrins to Ras, Rac1, and Cdc42 by promoting the formation of multimolecular complexes in the membrane, which leads to the up-regulation of adhesion-dependent small GTPase activation, Sensitization of human pancreatic cancer cells harboring mutated K-ras to apoptosis., Phospho-ERK may be a useful marker in combination with K-Ras for improving the prognosis of colorectal cancer., KRAS mutations in codons 12 and 13 of exon 2 in one hundred formalin-fixed paraffin-embedded (FFPE) colorectal cancer samples by three different methods, RAS mutations are frequent events in sporadic medullary thyroid carcinoma., Organs initially involved by distant metastasis were different according to the KRAS mutational status inmetastatic or recurrent colorectal cancer (MRCRC) patients., Assessment of the prognostic value of KRAS codon 12 and codon 13 mutations in tumor tissue from patients with advanced colorectal cancer using CAPOX or FUFOX treatment regimens., MSI status, KRAS and BRAF mutation rates varied remarkably among the colonic carcinoma subsites irrespective of right- and left-sided origin., in Japanese colorectal cancer patients the KRASp.G13D mutation had prognostic impact in relation to disease-free survival in stage I-III disease, while the prognosis of stage IV patients without anti-EGFR antibody therapy was unaffected by KRAS status., Codon 13 KRAS mutation is a negative predicitive tumor marker in colorectal carcinoma treated with combined antineoplastic agents., Red blood cell folic acid is significantly deficient in colorectal cancer patients with K-ras mutations., KRAS mutant subpopulations are present in a large number of thyroid tumors., heterogeneity in frequencies of KRAS/PIK3CA somatic mutations is consistent with already-reported discrepancies in distribution of germline mutations for other malignancies within Sardinian population., Data indicate that KRAS, BRAF, PIK3CA, and AKT1 mutations can be rapidly and accurately detected for cancer diagnosis., Data indicate that of the 32 cardio-facio-cutaneous syndrome (CFC) patients, 28 (88%) had a known mutation in a gene that is causative for CFC, including BRAF (n = 21), MEK1 (n = 2), MEK2 (n = 4), and KRAS (n = 1)., Data suggests that KRAS codon 12 mutation may not represent a homogeneous entity in metastatic colorectal cancer when treated with cetuximab-based first-line therapy., Data indicate that epiregulin (EREG) expression significantly correlated with KRAS expression or KRAS copy number in KRAS-mutant non-small-cell lung cancer (NSCLC) cell lines., A high frequency of KRAS gene mutations exists in Chinese patients with colorectal cancer, and are associated with poor survival, tumor differentiation and liver metastasis., metastatic colorectal cancer patients with the KRAS p.G13D mutation appeared to benefit more from cetuximab than patients who had tumors with KRAS codon 12 mutations, KRAS mutation is associated with response to therapy in non-small-cell lung cancer., K-ras mutation status and subtypes may be associated with survival duration in pancreatic cancer patients., Data show that Med23 RNAi specifically inhibits the proliferation and tumorigenicity of lung cancer cells with hyperactive Ras activity., no evidence for association between endometriosis risk and rs61764370 or any other SNPs in KRAS, KRAS mutation is suggested to be poor prognostic factors in CRLM., KRAS mutation is associated with early-stage low-grade endometrial cancers., A higher frequency of KRAS mutation G12C in women, their younger age, and lesser smoking history together support a heightened susceptibility to tobacco carcinogens., KRAS p.G13D mutations are associated with sensitivity to anti-EGFR antibody treatment in colorectal cancer cell lines., EGFR and downstream genetic alterations in KRAS/BRAF and PI3K/AKT pathways have roles in colorectal cancer and treatment [review], findings show intratumoral heterogeneity of KRAS mutational status is rare in non-small cell lung cancer (NSCLC); finding is in line with hypothesis that oncogenic activation of KRAS is an early event and a bona fide "driver mutation" in NSCLC, Baseline sPLA(2)IIa expression predicts response to sPLA(2)IIa inhibition in some K-ras mutant lung cancer cells., KRAS mutations were not detected in lung cancer patients harboring mutations in either EGFR or P53., This study provided further evidence for the prognostic importance of KRAS status in terms of recurrence-free and overall survival in patients with colorectal cancer liver metastases., a previously unknown link between activated K-Ras and menin, an important interplay governing tumor activation and suppression in the development of lung cancer., These data support the utility of the therascreen KRAS kit as a means of selecting patients who may benefit from cetuximab therapy., the spectrum and frequency distribution of the identified KRAS and BRAF mutations in Serbian patient with colorectal cancer are in good accordance with literature data., KRAS and BRAF mutations are infrequent or absent, respectively in Intestinal-type sinonasal adenocarcinoma, Diverging gain-of-function mechanisms of two novel KRAS mutations associated with Noonan and cardio-facio-cutaneous syndromes., KRAS G>A mutation is associated with relapse in duodenal adenocarcinoma., A meta-analysis was performed to compare KRAS gene mutations in colorectal cancer tissue samples with primary and metastatic colorectal cancers, Specific morphologic features in colon cancer suggest a higher likelihood of the presence of KRAS mutations. These morphologic features overlap partially with those associated with DNA mismatch repair gene mutations, Metastatic colorectal cancer patients with KRAS codon 13 mutations demonstrate a greater clinical response to anti-EGFR treatment than patients with other KRAS mutations [review], KRAS G12A is important for IL-2-independent growth of PLT-2 cells and suggests the possibility of involvement of KRAS mutation with disease progression., The low rate of K-ras and EGFR mutations, coupled with the high surface expression of EGFR, suggests similarity in the EGFR signalling pathway between Squamous cell anal carcinoma and squamous cell carcinoma of the head and neck., The results confirm a strong correlation between activating RAS mutations and nevus sebaceus., The findings provide evidence that HRAS and KRAS mutations are sufficient to cause nevus sebaceus without genome instability, LOH, or secondary mutation., Studied differential miRNA expression in metastatic colorectal cancer by microarrays from primary tumors of 33 patients who had wild-type KRAS/BRAF and third- to sixth-line anti-EGFRmAb treatment, with/without irinotecan., Ddata suggest that KRAS alterations are linked to clinical phenotypes in endometrial carcinomas with increase in copy-number and mRNA expression levels from primary to metastatic lesions., By identifying the KRAS mutational status at the metastasized colorectal carcinoma, a statement about the benefit of an anti-EGFR-therapy can be given, which is nowadays the basis of diagnostic and therapy of this cancer., In proximal colon lesions, the incidence of KRAS mutations is significantly higher in the granular-type than in the non-granular-type of colorectal laterally spreading tumor., QoL was evaluable in 627/666 patients (94%) with KRAS wild-type tumours; of these 52% received FOLFIRI, and 48% FOLFIRI plus cetuximab. Pattern mixture analysis revealed no significant differences., indicate that patients with mutant KRAS tumors fail to benefit from adjuvant chemotherapy and do not respond to EGFR inhibitors[review], One hundred and ten patients (51%) were identified who were potentially nonresponders to anti-EGFR therapy, High KRAS expression is associated with the proliferation and invasion of non-small cell lung cancer., Analysis of hypermethylation status of a panel of genes and KRAS mutation detection offer a similar diagnostic yield in the evaluation of pancreatic masses., Molecular characterization of single CTCs demonstrated considerable intra- and interpatient heterogeneity of EGFR expression and genetic alterations in EGFR, KRAS, and PIK3CA, ras-Induced up-regulation of CTP, KRAS gene mutation predict poor prognosis in colorectal cancer patients, treated with EGFR inhibitors., In Chinese colorectal carcinoma patients, KRAS mutations are associated with gender, age, tumor differentiation and primary tumor sites, Codon 12, 13 in KRAS gene and codon 600 in BRAF gene are the most common mutation points in Chinese colorectal cancer. KRAS and BRAF mutations are mutually exclusive. KRAS and BRAF gene mutation is higher in females than that in males., The detection rate of KRAS mutation is higher in female colorectal carcinoma patients than males. The presence of KRAS mutation does not significantly correlate with patients' age, tumor site, differentiation grades and histological types., KRAS mutation has no significant correlation with colorectal carcinoma patients' age, tumor site, tumor gross appearance, degree of differentiation, depth of invasion, TNM stages, lymphatic invasion, abdominal or distant metastases and prognosis., Intercellular transfer of mutant KRAS is a characteristic feature of invasive colonic cancer cells., KRAS mutations are found in up to 95% of pancreatic cancer cases., Studies indicate that only mutant KRAS codon G12A was associated with a negative predictive effect on overall survival (OS)., KRAS mutation status could be a novel biomarker for predicting disease recurrence in Japanese patients with stage II colorectal cancer ., there are conserved components of mutant K-Ras signaling and phenotypes but that many depend on cell context and environmental cues, Our findings suggest that RAS pathway activation due to BRAF V600E and KRAS mutations is an important event in a subset of peripheral nerve sheath tumours not related to neurofibromatosis, Kras mutation and p53 overexpression rates in pseudomyxoma peritonei are comparable to those of colorectal adenomas and mucinous colorectal cancer., The present study revealed that ESCC of Brazilian patients do not present mutations in hot spots of EGFR, K-RAS and BRAF and only a minor proportion present overexpression of EGFR or HER2., KRAS mutation is associated with lung cancer and is not associated with response to EGFR-tyrosine kinase inhibitors or chemotherapy., Activating GNAS mutations are often associated with KRAS mutations as a characteristic genetic feature of pyloric gland adenomas (PGAs) of the stomach and duodenum., Mutations affecting BRAF, EGFR, PIK3CA, and KRAS are not associated with sporadic vestibular schwannomas., We find that LDHB expression correlates to both KRAS genomic copy number gain and KRAS mutation in lung cancer cell lines and adenocarcinomas., Low-grade bladder papillary carcinoma is associated with mutation in the FGFR3 or in some cases mutations in RAS genes., Results support a role for the PAK4 and PAK1 in the proliferation of mutant KRAS-driven colorectal carcinoma cells via pathways not involving RAF/MEK/ERK and PI3K/AKT signaling, Evolutionarily conserved protein ERH controls CENP-E mRNA splicing and is required for the survival of KRAS mutant cancer cells., presence of KRAS mutations in plasma in advanced non-small cell lung cancer may be a marker of poor prognosis and may also hold predictive value., The prevalence of RAS mutations in the present series of medullary thyroid cancer (MTC) was 10.1%, and 17.6% when considering only RET-negative cases. RAS mutations were found in MTC tumor tissue but not in peripheral blood indicating their somatic origin, Laboratories and clinicians need to be aware of the decrease in correct mutation call rate proportionally with decreasing percentage of tumor cells and that external quality assurance schemes need to address low tumor cell percentage in the test samples., KRAS mutations were frequently identified in mucinous adenocarcinoma subtypes., collegiate smokers (former smokers who smoked between 101 lifetime cigarettes and 5 pack-years)with advanced-stage lung cancers represent a distinct subgroup of patients with a higher frequency of KRAS mutations and lower frequency of EGFR mutations compared with never smokers, This article presents the case of a 64-year-old patient with a glandular papilloma of the right main bronchus including the immunohistochemical and molecular work-up as well as a review of the current literature., Approximately 90% of medullary thyroid cancers had mutually exclusive mutations in RET, HRAS, and KRAS, suggesting that RET and RAS are the predominant driver pathways in medullary thyroid cancer., only one mutation (K-Ras codon 13; Gly to Asp) was detected among the 61 hepatocellular carinoma patients studied; findings indicated that the activation of Ras proto-oncogenes by mutations in codons 12, 13 and 61 does not play a major role in hepatocellular carcinogenesis, KRAS mutations, detected in pancreatic cyst fluid, are associated with mucinous cysts and progression and development of malignancy and should be considered in assessing pancreatic cysts., KRAS mutation is associated with esophageal squamous cell carcinoma., Findings indicate that K-RAS regulates both caveolin-1 expression and other factors affecting caveolin-1 functions in colon cancer-derived cell migration., KRAS mutations are not associated with early stage colorectal cancer., KRAS destruction by RC-U occurred through a ubiquitin-dependent, proteasome-mediated degradation pathway. RC-U inhibited pancreatic cancer cell growth in vitro and in vivo., we have shown that patients harbouring KRAS low frequency mutations benefit less than others from anti-EGFR therapy., Our results confirm the importance of point mutations in KRAS codons 12, 13, and 61 in the molecular pathogenesis of colorectal adenocarcinomas in the Turkish population., Quality control and assurance of KRAS genotyping is critical, and standardization of the methodology is warranted, FGFR2, KRAS and PIK3CA are frequently mutated in primary and metastatic endometrial lesions., EGFR mutation rate is related with gender, smoking history and pathological type in non-small cell lung cancer patients, and is also related with differentiation and smoking history in adenocarcinoma patients., About one third of patients with colorectal adenocarcinoma have KRAS gene mutation, which might be related to patients' gender., The status of EGFR and KRAS mutation in serum was not prognostic in patients with advanced non-small cell lung cancer, This study shows that 21% of Nigerian colorectal patients carry a KRAS mutation; half the rate in Caucasians., The G12C KRAS mutation is a strong negative predictor for EGFR-TKI treatment, whereas other KRAS mutation types have not negatively predicted treatment efficacy compared with that for the wild-type KRAS genotype., mutational status of N-RAS and K-RAS genes in a cohort of 504 Chinese acute myeloid leukemia patients; mutation frequency of N-RAS and K-RAS were 9.7 percent and 2.9 percent respectively; concluded RAS mutations are associated with some biologically specific subtypes of AML but don't impact clinical outcome in Chinese patients, Findings support the development of ISG15 conjugation inhibitors for treating breast and also other cancers expressing oncogenic Ki-Ras., the imbalance in expression of Aurora-A and BRCA2 regulates RAS-induced genomic instability and tumorigenesis, MicroRNA-31 activates the RAS pathway and functions as an oncogenic MicroRNA by repressing RAS p21 GTPase activating protein 1 (RASA1), KRAS mutations is associated with colorectal cancer., we demonstrate that oncogenic K-Ras is not constitutively active but can be readily activated by upstream stimulants to lead to prolonged strong Ras activity, prevalence of KRAS mutations was identified in patients with ICC, BilIN-3, and BilIN-2 compared with BilIN-1. Furthermore, KRAS mutations were detected in LBD lesions and PBG lesions, EGFR and KRAS mutational rates were comparable in primary and unpaired metastatic lung adenocarcinoma in pre-chemotherapy and postchemotherapy groups., The prevalence of EML4-ALK, EGFR status and KRAS mutations in 208 Chinese patients with non-small cell lung cancer, is reported., Report K-ras mutations in pancreatic ductal carcinoma and their relationship to patient survival., KRAS-mutated carcinomas frequently develop in contiguity with a residual polyp and show molecular features distinct from other colorectal carcinomas, in particular from tumors with neither BRAF nor KRAS mutation., Data indicate that the concordance between EGFR and KRAS mutational status in 29 paired scraped smears and needle washing was 100%, with 7 paired samples showing the same EGFR mutation and 8 paired samples showing the same KRAS mutations., sensitive, fast, and cost-effective screening method for KRAS mutations, and successfully detected low-abundance KRAS mutations in clinical samples, which will allow provision of more precise individualized cancer therapy., EGFR and KRAS mutations are frequent in adenocarcinomas and are not prognostic factors for survival., Data indicate that Ras inhibition by Salirasib (FTS) induced autophagy in several cell lines, including mouse embryonic fibroblasts and the human cancer cell lines HeLa, HCT-116 and DLD-1., BRAF and codon 12 KRAS mutations predict for adverse outcome of colorectal cancer patients receiving cetuximab., HB-EGF overexpression and Kras(G12D) together, but neither alone, increase cancer cell proliferation., Report KRAS mutations in ovarian serous carcinoma., KRAS mutations are associated with lung cancer., Mutations in genes pertaining to the canonical RAS pathway are found in a minority of adenoid cystic carcinomas, and that activating KIT mutations are either absent or remarkably rare in these cancers., study demonstrated that RAS mutations frequently occur in Mixed Lineage Leukemia (MLL)-rearranged infant acute lymphoblastic leukemia (ALL) cases and especially in t(4;11)-positive infant ALL patients and their presence represents an independent poor prognostic factor, KRAS is rather a prognostic than a predictive biomarker in pancreatic cancer, KRAS mutations in codon 13 have similar behavior as KRAS WT., cell-autonomous phosphoinositide 3-kinase and 3-phosphoinositide-dependent protein kinase 1 are key effectors of oncogenic Kras in the pancreas, mediating cell plasticity, acinar-to-ductal metaplasia, and pancreatic ductal adenocarcinoma formation, Data suggest that KRAS mutations in SW48 colorectal cancer cells are linked to resistance to sunitinib., Mutations in different KRAS codons may have different effects on rectal cancer resistance to neoadjuvant chemoradiation therapy, Down-regulated expression of K-Ras mRNA., This study confirmed that KRAS testing is definitely part of the management of most of metastatic colorectal cancer patients, despite discrepancies observed in the rate of prescription and the time of results., KRAS mutation is not associated with treatment response in rectal cancer., Data indicate that (4-Chloro-2-(piperidin-1-yl)thiazol-5-yl)(phenyl)methanone and (4-bromo-2-(piperidin-1-yl)thiazol-5-yl)(phenyl)methanone inhibited cell growth through inhibition of both alpha-1 Na(+)/K(+)-ATPase (NAK) and Ras oncogene activity., KRAS mutations are associated with solid predominant lung tumors., KRAS mutations are associated with metastatic lung adenocarcinoma., Wild-type copies of HRas, NRas and KRas play unique roles in the context of mutant KRas-driven tumors., The current study demonstrates that the presence of GNAS in combination with KRAS in pancreatic cystic fluid obtained by EUSFNA improves the sensitivity for diagnosis of intraductal papillary mucinous neoplasms, Data show that KRAS codon 12/13 mutations have negative prognostic value in metastatic colorectal cancer patients treated with FOLFOX/XELOX, but is not predictive of treatment benefit with cediranib, using progression-free survival and overall survival., Kirsten Ras (KRAS)-mutated CRC was associated with statistically significantly poorer survival after diagnosis than KRAS-wild-type CRC., Large multicentre study demonstrated that KRAS mutations and DNA MMR deficiency have a role in a small subgroup of gastric cancer., In patients with colorectal cancer expressing mutant KRAS, high levels of plasma KRAS was associated with early disease progression., KRAS mutation rate decreased from 4.6% (3/66) to 3.0% (2/66) with Neoadj-Chemo., KRAS as a prognostic marker of non-small-cell lung cancer (Review), There was no association between the mutations and expression pattern of K-ras, APC and p53 in colorectal cancer among Indians., colorectal tumor tissue was analyzed utilizing WAVE mutation analysis to determine if regions of the tumor display heterogeneity in the expression of mutated KRAS and if regions within tissue blocks uniformly display resistant or susceptible phenotypes, Examination of 6 PDACs revealed that 4 of 5 gastric-type IPMNs negative for GNAS mutations contained mutations in codon 12 of KRAS. Mutations in codon 13 of KRAS were not identified in PDACs and IPMNs., the reprogramming of glutamine metabolism is mediated by oncogenic KRAS, the signature genetic alteration in pancreatic ductal adenocarcinoma, through the transcriptional upregulation and repression of key metabolic enzymes in this pathway, Mutation status of KRAS is the same in primary colorectal neoplasms and metastasis., KRAS mutational status could have an impact to the decision to give chemotherapy or EGFR-TKIs as second-line treatment to patients with non-small cell lung cancer, mainly in patients harboring WT-EGFR., About one fourth of mCRC cases wild-type for KRAS codons 12 and 13 present other mutations either in KRAS, BRAF, or PIK3CA, many of which may explain the lack of response to anti-EGFR therapy observed in a significant proportion of these patients., TIMP1 is an upregulated gene product and a proliferative inducer of K-Ras(G12D)-mutated pancreatic ductal cells through the ERK2 signaling pathway., Breast tumors with KRAS codon 12 mutations seem to present a worse prognosis., DAB2IP expression was reduced in patients with pancreatic cancer compared with those with no cancer. DAB2IP expression was correlated with the KRAS gene, perineurial invasion and clinical stage of the disease., KRAS mutations are not associated with tyrosine kinase inhibitors treatment efficacy in non-small cell lung cancer., The association of survival in PDAC patients with CDKN2A aberrations in tumors was not statistically significant, the sub-group with concomitant KRAS mutations and CDKN2A alterations were associated with lower survival., Studies indicate that inhibition of targets outside the main KRAS signaling pathway, specifically the cell cycle related kinase PLK1, has been shown have an effect in cells that harbor mutant KRAS., Data show that somatic cell knockin of both KRAS G12V and oncogenic PIK3CA mutations in human breast epithelial cells results in cooperative activation of the phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways., Our findings suggest that in a subset of ductal adenocarcinomas, KRAS mutant allele-specific imbalance correlates with the progression to undifferentiated carcinoma of the pancreas., K-RAS mutations are associated with a worse overall survival in patients with non-small cell lung cancer, especially in patients with adenocarcinoma and early stage., presence of a K-ras gene mutation was a poor prognostic factor, K-RAS and B-RAF mutations do not seem to be predictive of treatment outcome as potential biomarkers for bevacizumab therapy in metastatic colorectal cancer., Identification of a novel association of KRAS mutations with solid growth pattern and tumor-infiltrating leukocytes in non-mucinous lung adenocarcinomas., This study demonstrated that either BRAF or RAS mutations were present in two thirds of follicular variants of papillary thyroid carcinomas and these mutations were mutually exclusive., findings demonstrate that the presence of a K-ras mutation correlated with high initial CEA and CA 19-9 levels in patients with metastatic colorectal cancer, KRAS mutation status is not a significant prognostic marker in patients with resected non-small-cell lung cancer., The mutational spectrum of KRAS exon 1 in bladder tumours, colorectal cancer (CRC) and chronic myeloid leukemia (CML), was analysed., KRAS mutations are associated with colorectal cancer., The KRAS mutation rate of Japanese colorectal cancer patients was 37.6%., A meta-analysis indicates that K-ras gene mutation analysis is useful for the differential diagnosis of pancreatic adenocarcinomas., Establishment of molecular subgroups based on KRAS and BRAF mutation status is important and should be considered in future prognostic studies in colorectal carcinoma., Mutational activation of KRAS does not seem to play any significant role in the development and progression of gastrointestinal stromal tumors., Cigarette smoking did not influence the frequency of KRAS mutations in lung adenocarcinomas in Korean patients, but influenced qualitative differences in the KRAS mutations., Results show that HDAC6 and SIRT2 regulate the acetylation state of K-RAS in cancer cells, These results suggested KRAS mutations have an independent prognostic value for chemotherapy in advanced non-small cell lung cancer., Adding panitumumab to irinotecan did not improve the overall survival of patients with wild-type KRAS tumours., We also examined 61 of our cases for the presence of PIK3CA, AKT1, PTEN and K-RAS mutations., There was significant association (p < 0.05) between KRAS mutations, age and the tumor differentiation., The T allele of the let-7 binding site polymorphism rs712 in KRAS 3' UTR was associated with a significantly increased risk of gastric cancer., Functional ALK rearrangements were mutually exclusive with EGFR and KRAS mutations in a large Western patient population. This lack of overlap was also observed in ALK-positive cancers with acquired resistance to crizotinib, Suggest that activating mutations of EGFR, HRAS, and KRAS contribute to the pathogenesis of human seborrheic keratosis., Report the role of KRAS mutations in the detection and classification of pancreatic mucinous neoplasms by endoscopic ultrasound fine-needle aspiration., we found that EVI1 upregulated KRAS expression through suppression of miR-96 in pancreatic cancer cells, Both the CRP single nucleotide polymorphism rs7553007 and KRAS/BRAF mutations were independent prognostic factors for colorectal cancer patients with synchronous liver metastasis., KRAS mutations are associated with colonic neoplasms., acquired EGFR and KRAS mutations do not constitute the main mechanism of resistance to anti-EGFR mAb, KRAS mutations are associated with colorectal neoplasms., KRAS mutation is associated with myelodysplastic syndromes and acute myeloid leukemia., KRAS mutation is not associated with response to chemotherapy in non-small-cell lung cancer., Taiwanese patients with metastatic colorectal cancer respond better to a cetuximab plus chemotherapy regime if their tumors have the wild-type KRAS gene, Sinonasal intestinal-type adenocarcinomas share common alterations of the EGFR pathway with colorectal adenocarcinomas, except for a lower frequency of KRAS and BRAF mutations., demonstrated associations of KRAS mutations with well-differentiated and mucinous ovarian carcinomas., Race was not statistically significantly associated with KRAS mutational status in patients with non small cell lung cancer., KRAS mutations are associated with lung cancer., These findings indicate that KRAS/MAPK1 amplification is critical for the growth of a subset of type II ovarian carcinomas., This study investigated the impact of KRAS, NRAS, BRAF, PI3KCA and TP53 status on outcome of elderly metastatic colorectal cancer patients, An antisense oligonucleotide specific to a K-ras point mutation promotes apoptosis in PC-2 cells., Gallbladder cancer has a high frequency of K-ras codon 12 mutation with poorer outcomes in resected stage II and III disease., KRAS mutations,found in smokers, are often activated in lung cancers, with mutations in about 20% of NSCLCs. Most are single amino acid substitutions in codons 12, 13, or 61. It is a negative marker for the efficacy of EGFR TKI in patients with NSCLC, Summing up the results about the KRAS and the BRAF mutation carriers from our study, the portion of potentially non responsive colorectal cancer patients for the anti-EGFR treatment is 28.26%., Higher frequency of k-ras mutations are associated with endometrial carcinomas with significant mucinous differentiation., KRAS mutations are associated with response to chemoradiation in rectal cancer., loss of RASSF1A may be involved in pathogenesis of colorectal cancer (CRC), its expression was found predominantly in K-ras wild-type CRCs., Colorectal cancer patients with low abundance of KRAS mutation may benefit from EGFR antibody therapy., Data indicate that p38delta mediates oncogene-induced senescence through a p53- and p16(INK4A)-independent mechanism., we did not find a correlation between the presence of a K-ras mutation and the presence of Epiregulin and Amphiregulin in colon cancer tissue., KRAS G12C mutations were associated with primary lung adenocarcinoma, whereas KRAS G12R mutations favored pancreatic adenocarcinoma, our findings suggest that loss of CDKN2A and, to a lesser extent, KRAS and PIK3CA somatic mutations have a role in the progression of a benign to an atypical proliferative Brenner tumor, Findings support the development of CDK and Raf co-targeting strategies in EGFR/HER-2-overexpressing or RAS/RAF mutant breast cancer (BC)., evaluated mutations in four driver genes, epidermal growth factor receptor (EGFR), Kirsten ras oncogene (KRAS), c-MET, and echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK), in Chinese lung adenocarcinoma patients, There was no difference in overall survival after starting EGFR-TKI in patients with KRAS mutation and EGFR/ KRAS WT., The brain microenvironment negatively regulates miRNA-768-3p to enhance K-ras and promote metastasis., The frequencies of EGFR, KRAS, BRAF, and HER-2 mutations in BM-NSCLC were 2.6, 38.5, 0, and 0% respectively. The incidence of KRAS mutation was significantly higher in female and younger patients., The frequencies of somatic EGFR, KRAS, and ALK gene abnormalities reflect the diverse ethnicity and smoking patterns of non-small-cell lung cancers patients in the United States., In patients with pancreatic ductal adenocarcinoma, solute carrier transporter (SLC) levels were not found to be associated with KRAS mutation status in exon 2, a complex regulatory system involving TP53, KRAS, and let-7a, This case to be the first description of a solitary serrated polyp with KRAS mutation, similar to the lesions occurring as polyposis in longstanding IBD, KRAS mutations with synchronous TP53 mutations occur predominantly in low-grade mucinous carcinomas, suggesting a specific molecular background of this ovarian cancer type., A let-7 KRAS rs712 polymorphism increases colorectal cancer risk., There was a negative correlation between KRAS codon 12 mutations and the level of HLA class I antigens in primary and metastatic tumors., KRAS mutations are associated with colorectal neoplasms., No associations were found with CRC harboring G>T mutations in KRAS/APC., in lung adenocarcinomas, KRAS mutations are prevalent in male smokers; EGFR mutations are associated with female sex, nonsmoking and lepidic and micropapillary growth; TTF1 has a role in survival; BRAF mutations have roles in survival, The KRAS rs712 polymorphism in let-7 miRNA binding site has no association with nasopharyngeal carcinoma risk., Stem cells with Kras(G12D) activation and Smad4 depletion can produce tumors that are multipotent and susceptible to epithelial mesenchymal transformation and metastasis., frequency of K-RAS mutations in the Puerto Rican population studied was 39 percent and mutant K-RAS was associated with advanced colorectal cancer stage, mucinous histotype and ulcerated tumors, mutations in KRAS codon 61, KRAS codon 146, BRAF, NRAS, or PIK3CA detected in Asian patients were not predictive of clinical benefits from cetuximab treatment., Data indicate that dual targeted inhibitors of PI3K/mTOR in combination with inhibitors of RAS/ERK signalling as a potentially effective approach to treating ovarian cancer., Clinical relevance of KRAS mutations in predicting the efficacy of cetuximab-containing therapy for metastatic colorectal patients in the Japanese population., KRAS/NRAS mutation predicts early lung recurrence and worse survival after curative resection of colorectal liver metastases., abnormal [beta]-catenin expression showed an inverse relationship with the presence of KRAS mutations in ovarian endometrioid adenocarcinoma, Primary and recurrent anal cancer expresses wild type KRAS, unaffected by treatment, supporting trials targeting EGFR in poor risk/recurrent anal cancer., RAS mutations, in addition to KRAS exon 2 mutations, predict a lack of response to anti-EGFR therapy in patients with metastatic colorectal cancer., Data indicate that differentially expressed IL-17, IL-22, and IL-23 levels are associated with K-ras in a stage-specific fashion along colorectal cancer progression and an association was established between mutant K-ras and GM-CSF and IFN-gamma., Report analysis of KRAS mutations in non-small cell lung carcinomas., Driver mutations among never smoking female lung cancer tissues in China identify unique EGFR and KRAS mutation pattern associated with household coal burning., KRAS mutations were associated with poorer overall survival of patients with pediatric B cell precursor acute lymphoblastic leukemia., KRAS mutation status does not seem to represent a strong prognostic variable., no significant associations have been detected between KRAS mutations and clinicopathologic variables and MSI in Tunisian patients as previously reported., Review/Meta-analysis, KRAS status was an independent predictor of overall and recurrence-free survival., 7 KRAS mutations were detected in adult Korean patients with acute myeloid leukemia; most common mutation was G-to-A transition in the second base of KRAS codon 13; study could not find any statistical differences of clinical features according to KRAS mutaion status, study demonstrated that mucinous adenocarcinomas with KRAS mutations have clinicopathologic characteristics different from those of mucinous adenocarcinoma without such mutations, KRAS gene mutations were found in 4 (5%) of 28 patients with squamous cell anal cancer, KRAS mutation impairs the therapeutic effect exerted by cetuximab-mediated antibody-dependent cellular cytotoxicity, Of 54 intrahepatic cholangiocarcinoma cases, 7.4% were mutant for KRAS, 7.4% were mutant for BRAF, and these were mutually exclusive. These cases were associated with a higher tumor stage and a greater likelihood of lymph node involvement., When genotypes of BRAF/KRAS mutated s-BOTs and corresponding implants were compared, no patient presented with a fully matching mutation profile of s-BOT and all corresponding implants., KRAS mutations are associated with non-small-cell lung cancer., Studies suggest that understanding the underlying biology of tumor-stroma interactions and tumor heterogeneity are critical to guiding rational approaches to designing treatments tailored to targeting KRAS in the stroma-rich microenvironment., miR-27a suppresses tumorigenesis of esophageal squamous cell carcinoma by targeting KRAS., Despite the overlapping clinical features, Rasopathy syndromes exhibit unique fenotypical features and the precise molecular diagnostics may lead to confirmation of each syndrome., Report role of KRAS oncogenetic risk classification in the prognosis of adult T-cell acute lymphoblastic leukemia., Androgen-induced AR activating signal upregulates let-7a that targets CMYC and KRAS and contributes to ER-, PR-, AR+ breast cancer pathogenesis., The presence of KRAS mutation in both mucinous adenocarcinoma and complex mucinous changes indicates that KRAS mutational activation is implicated in the pathogenesis of a significant subset of endometrial mucinous carcinoma., This review will focus on the current (EGFR and KRAS mutations)and future biomarkers in the advanced NSCLC field and also address potential related targeted therapies for these patients., Data indicate that coexistence of EML4-ALK fusion or ALK copy number increase and EGFR, MET, and KRAS mutations in tumor tissue from two treatment-naive Chinese non-small cell lung cancer (NSCLC) patients., K-ras gene mutation is not associated with response to chemotherapy in colorectal cancer patients., overall genomic and transcriptional landscape of lung adenocarcinoma is affected, but only to a minor extent, by EGFR and KRAS mutation status, RAS is the most frequently mutated oncogene in cancers. Isoprenylcysteine carboxylmethyltransferase (ICMT) methylates RAS and other CaaX-containing proteins., The presence of K-Ras mutations has prognostic value in colon cancer patients, and also predicts the responsiveness to inhibitors of EGFR signaling., KRAS mutations are associated with proliferative thyroid lesions., Case Report, Ras regulates KIF2C to control cell migration pathways in transformed human bronchial epithelial cells., Here we report a sensitive and inexpensive assay for KRAS mutations based on a PNA-mediated PCR clamping., The combination of lenalidomide and cetuximab appeared to be well tolerated but did not have clinically meaningful activity in KRAS-mutant metastatic colorectal cancer patients., Differences in the regulation of K-Ras and H-Ras isoforms by monoubiquitination., Prognosis after progression to firstline FIr-B/FOx may be significantly favourable in MCRC pts re-challenged with intensive regimens, and unfavourable in c.35 G>A KRAS mutant patients., Data indicate that sp-Erf2/zDHHC9 palmitoylates Ras proteins in a highly selective manner in the trans-Golgi compartment to facilitate PM targeting via the trans-Golgi network, a role that is most certainly critical for Ras-driven tumorigenesis., the joint presence of CDKN2A methylation and KRAS mutations independently predicted recurrence of cancer and was associated with poor overall and cancer-specific survival., Tumor KRAS has minor clinical impact, whereas plasma KRAS status seems to hold important predictive and prognostic information., We show that loss of Scrib and activated oncogenic KRas cooperate in vivo, resulting in more aggressive lung tumors, KRAS mutations are at high risk for early pulmonary recurrence in colorectal carcinoma., Results suggest that the cancer-associated rs61764370 variant exerts a biological effect not through transcriptional modulation of KRAS but rather by tuning the expression of the microRNA let-7., Study reveals functional and mechanistic links between miRNA-30b and oncogene KRAS, PIK3CD and BCL2 in the pathogenesis of colorectal carcinoma., Mutant KRAS is a druggable target for pancreatic cancer., identified inositol trisphosphate receptors as unique effectors of K-Ras4B that antagonize the prosurvival signals of other K-Ras effectors., GNAS and KRAS mutations are common in intraductal papillary neoplasms of the bile duct, KRAS mutation did not have prognostic value in patients with metachronous or synchronous metastatic CRC., mutation patterns are quantitatively and qualitatively distinct between non-small-cell lung cancer and colorectal cancer, KRAS mutation did not reduce sensitivity to bortezomib or dexamethasone in myeloma patients., Degradation of activated K-Ras orthologue via K-Ras-specific lysine residues is required for cytokinesis., Oncogenic K-Ras and loss of Smad4 mediate invasion by activating an EGFR/NF-kappaB Axis that induces expression of MMP9 and uPA in human pancreas progenitor cells., The detection of activating somatic mutations in gene KRAS using pyrosequencing technique, This study is the first to compare different SMIs in combination with IR for the treatment of K-RAS mutant rectal cancer, and our findings suggest that Chk1/2 inhibitors should be evaluated in new clinical trials for LARC., A protumorigenic role for CLPTM1L that is critical for Ras-driven lung cancers, with potential implications for therapy and chemosensitization., Findings suggest that miR-200c is a potent inhibitor of tumor progression and therapy resistance, by regulating a multitude of oncogenic pathways including the RAS pathway., Small G proteins Rac1 and Ras regulate serine/threonine protein phosphatase 5 (PP5).extracellular signal-regulated kinase (ERK) complexes involved in the feedback regulation of Raf1., KRAS requires S181 phosphorylation to manifest its oncogenic properties, implying that its inhibition represents a relevant target to attack KRAS-driven tumors., correlation between KRAS or BRAF mutations and prognosis was not observed, The PI3K/AKT pathway promotes gefitinib resistance in mutant KRAS lung adenocarcinoma by a deacetylase-dependent mechanism., KRAS gene mutation is not associated with chronic myeloid leukemia., Smad4 represents a barrier in KRAS-mediated malignant transformation of the near normal immortalized human pancreatic duct epithelial (HPDE) cell, Oncogenic KRAS plays a central role in controlling multiple metabolic changes such as stimulation of glucose uptake, differential channeling of glucose intermediates, reprogrammed glutamine metabolism, increased autophagy, and macropinocytosis. (Review), High KRAS mRNA expression is associated with non-small-cell lung cancer growth and progression., results suggest that the frequency of wild-type KRAS in cancer associated with familial adenomatous polyposis was approximately 40%, although it was lower than that in sporadic cancer, the first BRAF V600/601 and KRAS G12-K16 screening study in primary mediastinal B-cell lymphoma that failed to identify hotspot mutations in this specific subtype, Identification of double-stranded genomic DNA spanning all chromosomes with mutated KRAS and p53 DNA in the serum exosomes of patients with pancreatic cancer., The suppression of K-ras expression by siRNA interfered with this synergism and inhibited both EGFR and Akt activity in A549 cells., As second- or later-line treatment of patients with KRAS-mutated metastatic colorectal cancer., Sag is a Kras-cooperating oncogene that promotes lung tumorigenesis, results indicate that serrated lesions of the appendix often harbor KRAS mutations rather than BRAF mutations and suggest that the serrated pathway in the appendix is likely different than in the colon and rectum, mutations result in lower disease control rate after the first-line platinum-based chemotherapy, Results identify miR-134 as a novel RTK-regulated tumor-suppressive hub that mediates RTK and RTK-inhibitor effects on GBM malignancy by controlling KRAS and STAT5B., KRAS mutations are more common in African Americans than among Caucasians and are associated with advanced stage in colorectal cancer patients., A KRAS somatic mutation was identified in 25% (7/28) of the TP53 mutated tumors, KRAS gene was wild type in 18 cases, whereas one mucinous carcinoma harboured a point mutation at codon 12, Knockdown of ACK1 abrogated bosutinib-induced inhibition of cell migration and invasion specifically in KRAS mutant cells. This finding was further confirmed in an in vivo zebrafish metastatic model, Studies suggest the potential predictive role of mutant KRAS in the context of chemosensitivity of non-small-cell lung cancer (NSCLC) which may depend on the individual drug types., KRAS (G-->A) mutation does not affect in vivo anti-cancer efficacy of cetuximab in gastric cancer xenograft model., Co-transduction of Kras(G12D) and AML1/ETO induces acute monoblastic leukemia., K-Ras mutation activates CSCs, contributing to colorectal tumorigenesis and metastasis in CRC cells harboring APC mutations. Initial activation of beta-catenin by APC loss and further enhancement through K-Ras mutation induces CD44, CD133, CD166 expression., systemic delivery of MNPsiCDK4 significantly inhibited tumor growth in an A549 NSCLC xenograft murine model, with depressed expression of CDK4 and mutational KRAS status., GNAS mutant colon tumors commonly have synchronous mutations in KRAS., This study investigated the proteome modulated by oncogenic KRAS in immortalized airway epithelial cells., expression of oncogenic KRAS shifts the balance of DNA repair toward the highly error-prone alternative nonhomologous end-joining pathway., Oxaliplatin-based regimens are more beneficial in KRAS mutant than in KRAS wild-type metastatic colorectal cancer patients., ADM is a new target of oncogenic KRAS in the setting of hypoxia, 42% of colorectal cancer tissue samples had KRAS mutations. Their frequency and distribution are similar to those reported in the literature, except for G12C mutation, Wild-type H- and N-Ras promote mutant K-Ras-driven tumorigenesis by modulating the DNA damage response., we review the latest published literature specific to KRAS mutation testing techniques--{REVIEW}, RAD21 expression in CRC is associated with aggressive disease especially in KRAS mutant tumours and resistance to chemoradiotherapy., KRAS mutations in ovarian serous borderline tumour are associated with recurrent low-grade serous carcinoma., rs712, rs9266, and one novel variant may have a functional role in regulation of KRAS by disrupting complementary sites of various miRNAs, including let-7 and miR-181., Although the sensitive pyrosequencing method was used, no EGFR, KRAS or BRAF mutations could be found, Our findings suggest that IL-8 expression is associated with certain clinicopathological features including age and is a potent prognostic marker in lung adenocarcinoma, especially in oncogenic KRAS-driven adenocarcinoma., RAS mutations beyond KRAS exon 2 and 3 were identified in 17% of locally advanced rectal cancer patients., KRAS gene insertions represent a diagnostic and clinical challenge due to the difficult and unusual pyrosequencing findings and the lack of information regarding its clinical impact., Activating KRAS mutations were associated with lung cancer., After activating hK-rasG12D gene expression, hK-rasG12D transgenic goat fetal fibroblast cells were transformed into tumorgenesis cells., In prostate cancer, EGFR mutations occur more commonly than KRAS mutations and EGFR and KRAS mutations may be mutually exclusive, In this cetuximab-treated colorectal cancer population, EGFR gain was associated with better outcome and PTEN protein expression with longer TTP in KRAS WT, KRAS WT/AREG high and KRAS/BRAF WT subpopulations, The inflammatory cytokine TNFalpha cooperates with Ras in elevating metastasis and turns WT-Ras to a tumor-promoting entity in MCF-7 cells., Mutations of the KRAS gene (exon 2) were detected in 36.3% of cases of CRC, more often in women (41.1%) than in men (31.2%). 8 different types of KRAS mutations were identified, the most frequent replacement of G12D (33.7%), G12V (32.7%) and G13D (12.5%), No correlation was found between the frequency of cancer recurrence and KRAS mutations in surgical margins, Findings demonstrated that oncogenic K-Ras activates the signaling cascade p38/PDPK1/PKCdelta/p47(phox)/NOX1 for ROS generation and consequent malignant cellular transformation., KRAS and BRAF genes were wild-type in all squamous cell anal carcinoma cases., study found incidence of KRAS mutations in metastatic colorectal cancer (mCRC) was similar to that of non-mCRC as previously reported; KRAS codon 13 mutations might be associated with younger female patients with mCRC, The KRAS mutation rate is significantly higher in women than in men and tumors on the right colon have a higher frequency of KRAS mutations than those on the left., Blockade of autophagy results in a mutant KRAS-dependent senescence-to-apoptosis switch in cancer cells treated with IR and erlotinib., No patients exhibiting phospho-S6rp-positive staining and an activating KRAS mutation demonstrated a prolonged response of everolimus in endometrial cancer., Increased KRAS mutation is associated with colorectal cancer progression and poor response to therapy., Mutations in KRAS exons 3 and 4 predict resistance to anti-EGFR therapies., K-ras mutations are common among the Saudi colorectal cancer population, especially pG12V and pG12D in codon 12, and are more frequent in sigmoid and rectal adenocarcinomas and stage IVB tumors., Results support the role of KRAS mutational status in pancreatic cancer biology and suggest may serve as prognostic marker., KRAS mutations in either codon 12 or 13 are associated with inferior survival in patients with resected stage III colon cancer, we identify altered regulation of folate metabolism in KRAS-mutant NSCLC cells that may account for higher antifolate activity in this subtype of NSCLC., KRAS mutations are more common in heavy smokers, and lung adenocarcinomas with KRAS mutation are more likely to invade the visceral pleura., Embelin suppresses growth of human pancreatic cancer xenografts, and pancreatic cancer cells isolated from KrasG12D mice by inhibiting Akt and Sonic hedgehog pathways., Enhanced KRAS activity increases bovine herpesvirus 1 oncolytic capacity in cancer cells., Mutations in KRAS were associated with rectal cancer., The SMURF2, Data shows that KRAS genotype, specifically the c.35 G>A KRAS mutation, may indicate poor prognosis in metastatic colorectal cancer patients., In a Brazilian cohort of patients with metastatic colorectal cancer, tumors had overall percentage of wild-type and mutated KRAS was 62.8% and 31.9%, respectively, with a greater percentage in women., Reexpression of Let-7g microRNA inhibits the proliferation and migration via K-Ras/HMGA2/snail axis in hepatocellular carcinoma., A let-7 microRNA-complementary site (LCS6) polymorphism in the 3' untranslated region of the KRAS gene has been shown to disrupt let-7 binding and upregulate KRAS expression in colon cancer., The KRAS-variant may be a genetic marker of risk for type 2 endometrial cancers., In cytogenetically normal acute myeloid leukemia, activating K-RAS mutations in codons 12, 13, or 61 were detected in 3 of 204 patients. Activating K-RAS mutations may cooperate with mutated NPM1 to induce leukemia., From a practical perspective, small biopsies may not adequately represent a tumor's full mutational profile, particularly for later arising but prognostically important mutations such as those in the KRAS and BRAF genes, Integrin alpha(v)beta expression and the resulting KRAS-RalB-NF-kappaB pathway were both necessary and sufficient for tumour initiation, anchorage independence, self-renewal and erlotinib resistance., kras and p53 undergo separate pathways in colorectal tumorogenesis. Interestingly, mutations in the K-ras gene might be considered a valuable prognostic factor correlated to poor outcome, The loss of the wild-type KRAS allele may be a common secondary genetic change in KRAS-related JMML and may affect the differentiation behavior of early JMML progenitors., Two (15%) of 13 patients with MTS were found to harbor a KRAS mutation and loss of MLH1 expression, While KRAS mutation status per se is neither prognostic nor predictive in stage III-IV lung adenocarcinoma, subtype-specific analysis may indeed identify clinically relevant subgroups of patients that may ultimately influence treatment decisions., This study indicated that mutations of KRAS, PIK3CA and NRAS were rare in advanced gastric cancer., study failed to promote (18)F-FDG PET/CT uptake as a surrogate examination for KRAS mutation testing, Implementation of KRAS testing did not influence CRC OS. Our data support the use of KRAS testing to guide administration of EGFR inhibitors for treatment of metastatic CRC without diminished OS., KRAS mutations are associated with colorectal cancer., PS detection of low-frequency mutations may improve the KRAS predictive value for EGFR therapy selection., findings identified Yap as a critical oncogenic KRAS effector and a promising therapeutic target for PDAC and possibly other types of KRAS-mutant cancers, Characteristics and prognosis of colorectal cancer with NRAS mutations are different from those with KRAS or BRAF mutations., The frequency of KRAS mutations in metastatic colorectal cancer reported by the major Australian test sites is very similar to that reported by other large overseas studies., Case Report, RAC1b overexpression constitutes a marker of poor prognosis in KRAS/BRAF WT mCRC patients treated with first-line FOLFOX/XELOX therapy., Rasfonin is a robust inhibitor of pancreatic cancers with the K-ras mutation., Data show that patients with a mutation in KRAS codon 13 experienced worse outcome than those with a mutation in KRAS codon 12 but both mutations are associated with a significantly higher mortality., The high-resolution melting method developed was shown to be a reliable method for KRAS mutation detection, APC, KRAS, and TP53 gene mutations were more common in colorectal cancer than in stomach cancer, Chinese colorectal cancer patients with either KRAS or PIK3CA mutations are more susceptible to distant metastasis., A KRAS or NRAS mutation was found in 31% and 62% of benign hyperplastic thyroid nodules and follicular thyroid carcinomas respectively., EGFR and KRAS mutations were present in adenocarcinoma of the lung but not squamous tumors., There were no clearly pathogenic mutations in the KRAS gene in a cohort with thymic tumors., Using an inducible RAS expression system, we show that overexpression of RAS disrupts the circadian clock and leads to an increase of the circadian period while RAS inhibition causes a shortening of period length., Results demonstrated that the SPACE-HRM system we set up is a high sensitive assay that can be used for EGFR and KRAS allele enrichment and reliable detection, Tumors with KRAS mutations in codons 61 and 146 account for an appreciable proportion of colorectal cancers., Simultaneous diagnostic platform of genotyping EGFR, KRAS, and ALK in 510 Korean patients with non-small-cell lung cancer highlights significantly higher ALK rearrangement rate in advanced stage., In 14 % of ovarian clear cell carcinomas, a KRAS mutation occurs in codon 2 exon 2., KRAS mutation is associated with high-risk stage II colon cancer., This helps to clarify the confusing body of literature regarding the clinical implications of the KRAS-LCS6 genetic variant on colorectal cancer outcomes, indicating that it should not be used to personalize therapeutic strategies., KRAS-mutation is associated with non-small cell lung cancer., Our results suggest that the presence of a KRAS mutation in colorectal carcinoma is associated with alterations in the nuclear morphometric properties of contrast and ellipticity., KRAS mutations are known to promote the emergence of aggressive subclones in the evolution of colorectal cancer., miR125a loss may have a role in k-ras dependent lung carcinogenesis, The results from this prospective cohort study further support an influence of sex and lifestyle factors on different pathways of colorectal carcinogenesis, defined by KRAS and BRAF mutation status of the tumours., KRAS CRC regulates MEK-dependent, ADAM17-mediated shedding of soluble decoy MET., Report no KRAS mutations in thyroid carcinoma showing thymus-like elements., Amplified PAK1, as well as KRAS amplification/mutation, may represent unique opportunities for developing targeted therapeutics for the treatment of gastric cancer., KRAS mutation is associated with pancreatic mucinous cysts., KRAS mutations are associated with response to chemotherapy in cancer., Data suggest that the K-Ras - JNK1/2 axis could be a potential target in cancer stem cells (CSCs) or proliferating cancer stem-like cells (CSLCs)-directed therapies against pancreatic cancer., Findings indicate that KRAS mutations at codon-12 are associated with different metabolomic profiles that might affect the responses to cancer treatments., Using a colon cancer cell line, study found 147 genes that promoted survival upon KRAS suppression. In particular, the transcriptional coactivator YAP1 rescued cell viability in KRAS-dependent cells upon suppression of KRAS and was required for KRAS-induced cell transformation., K-RAS Mutation is associated with non small cell lung cancer., KRAS codons 12 and 13 mutation status was the first validated molecular biomarker for anti-EGFR antibodies, Studies indicate that K-RAS gene mutations cause GTPase RAS to remain locked in constitutively active signals through the downstream cascades leading to proliferation., Variable KRAS mutations may have different effects on colon cancers; further studies are needed to verify these results, The frequency and characteristics of KRAS gene mutation in Turkish non-small cell lung cancer patients, Non-invasive QTA can differentiate the presence of K-ras mutation from pan-wildtype NSCLC and is associated with patient survival., Activating FGFR2-RAS-BRAF mutations play a critical role in the pathogenesis of most cases of ameloblastoma., EGFR or KRAS mutations were detected with xTAG liquidchip technology, In KRAS-dependent pancreatic ductal adenocarcinoma cell lines, HNRNPA2B1 interacts with and regulates the activity of KRAS G12V and G12D., significant KRAS mutation discordance between the adenoma and carcinoma component of the colorectal tumor lesion., up-regulation of KIF2C and KIF2A by ERK1/2 caused aberrant lysosomal positioning and mTORC1 activity in a mutant K-Ras-dependent cancer and cancer model., Report high concordance rate between next generation sequencing and standard testing for KRAS., Clinicopathologic characteristics, survival outcomes, functional impact, and gene expression profiling were similar between patients with KRAS 12/13 and those with NRAS or KRAS 61/146-mutated colorectal cancers, In tDNA, 50 mutations (36 EGFR, 5 ERBB2, 4 KRAS, 3 BRAF, and 2 PIK3CA) were identified, of which 26 were detected in cfDNA. These data demonstrate the feasibility and potential utility of mutation screening in the detection of a range of tumor biomarkers, These data suggest that disabling of the G1 Q checkpoint could represent a novel vulnerability of cancer cells harboring K-Ras and possibly other mutations that disable the Q-dependent checkpoint., results indicate MTH1 is a novel and critical component of oncogenic KRAS-associated malignancy and its inhibition is likely to yield significant tumor-suppressive outcomes in KRAS-driven tumors., We sought to investigate whether mucinous features, such as signet-ring cell feature and extracellular mucin, are associated with EGFR and KRAS mutations in patients with lung adenocarcinoma, oncogenic K-ras and downregulated p16/INK4A in human pancreatic tumorigenesis, Current approaches for predicting a lack of response to anti-EGFR therapy in KRAS wild-type patients., The adenocarcinoma showed expression of CK20 and p53, but CK7 in patches. The molecular profile of the adenocarcinoma showed a mutation in KRAS and wild-type BRAF, which might be associated with malignant transformation of intracranial mature teratomas., Only one (2.8%) had a K-ras mutation., KRAS mutations were detected in 13.6% of the colorectal cancer precursor lesions, namely in adenomas and in hyperplastic polyps, but in no serrated adenoma. In CRC cases, 46.8% exhibited KRAS mutation., Oncogenic KRAS upregulated mir31 in lung carcinogenesis., study surveyed the ability of 12 different oncogenic KRAS mutations to induce pancreatic tumors in an in vivo tumorigenesis assay; results suggest the spectrum of KRAS mutations observed in human pancreatic cancer reflects selection based on variable tumorigenic capacities, including ability to activate MAPK/ERK signaling, Neuronal NF1/RAS regulation of cyclic AMP requires atypical PKC zeta activation, which is perturbed in neurofibromatosis type 1., KRAS, BRAF, and PIK3CA mutations were evaluated in 204 colorectal carcinoma samples; the frequency of KRAS, BRAF, and PIK3CA mutations was 23.5, 9.8, and 5.9 %, respectively., Data indicate that high KRAS gene expression corresponded to low survival rates., The TG/GG rs61764370 KRAS-variant is a potential predictive biomarker for poor platinum response in recurrent/metastatic head and neck squamous cell carcinoma patients, A mutually exclusive pattern of FGFR2, HER2, and KRAS gene amplification and survival trends in gastric cancer patients., The presented data subclassified colorectal cancers (CRCs) based on their activated signaling pathways and identify a role for c-MET and IGF1R-driven PI3K signaling in CRCs, which is superior to KRAS mutational tests alone., in pancreatic undifferentiated rhabdoid carcinomas the pleomorphic giant cell subtype is characterized by KRAS alterations and the anaplastic monomorphic subtype correlates with the absence of KRAS alterations, NRAS and KRAS mutations have a role in Down syndrome acute lymphoblastic leukemia that lacks JAK2 mutations, DNa mutational analysis in lebanese population shows that mutations of EGFR and KRAS are present in 8.5% and 37.7% respectivement in lung adenocarcinoma., KRAS is an independent prognostic marker in resected stage I lung adenocarcinoma. Differential outcomes are associated with codon and amino acid specific KRAS mutations., The variant G-allele of the KRAS-LCS6 polymorphism was significantly associated with better overall survival in patients with oropharyngeal squamous cell carcinoma, Thyroid nodules with KRAS mutations are different from nodules with NRAS and HRAS mutations with regard to cytopathologic and histopathologic outcome characteristics., Inhibition of proliferation by K-RAS depended on antiproliferative RAS effector RASSF1A and blockade of the RAS-activated proproliferative RAF/MAPK pathway by tumor suppressor menin, KRAS showed a direct connection to numerous cancer-related pathways, such as MAPK signaling pathway, suggesting that it may be a central communication hub in breast cancer., KRAS mutations in serial blood samples revealed that individual patient's circulatin tumor cells exhibited different mutational status of KRAS during treatment., The cumulative incidence of bone, brain, and lung metastases was significantly higher for patients with KRAS MUT compared with those with KRAS WT., Meta-analysis found that cetuximab objective response rate (ORR) of metastatic colorectal cancer (mCRC) patients with KRAS mutation was 8%, whereas the ORR of mCRC patients with wild-type KRAS was 34%., KRAS oncogene mutations originated from the guanosine nucleotide and over half of all transversions in lung cancer and colorectal cancer were c.34 G>T and c.35 G>T, respectively. c.35 G>A was the most frequent type of transition in both cancers., Targeted sequencing on primary, metastatic, and normal tissue from colorectal cancer patients found a high degree of concordance for KRAS, NRAS, and BRAF mutations that were identical in both the primary and metastatic tumors., KRAS mutational subtype and copy number is associated with in vitro response of pancreatic cancer cell lines to MEK inhibition., LCS6-variant (of the KRAS gene) patients with metastatic colorectal cancer have an excellent response to anti-EGFR mAb monotherapy, without any benefit from the addition of chemotherapy., KRAS (41%) and PIK3CA (8%) mutations in Colorectal cancer in patient-derived xenograft models closely paralleled patient tumors (35 to 51% KRAS, 12 to 21% PIK3CA)., These results supported the role of the KRAS rs712 polymorphism as a potential genetic biomarker for the extension of papillary thyroid cancer., expression of K-Ras and RalB and possibly RalA proteins is critical for maintaining low levels of p53, and down-regulation of these GTPases reactivates p53 by significantly enhancing its stability, contributing to suppression of malignant transformation, A higher number of gene mutations and the DAXX/ATRX and KRAS gene mutations are correlated with a poor prognosis of Chinese patients with pancreatic neuroendocrine tumors., No relation was found between the K-ras oncogene mutation and reduced survival, in contrast to what has been established in the international medical literature, NQO1 expression was significantly more frequent in non-small cell lung carcinoma patients with KRAS mutations, suggesting that oxidative stress may be important in the pathogenesis, worse prognosis, and resistance to treatment reported in these patients., LKB1 CN in combination with KRAS mutation predicted brain metastasis in NSCLC., KRAS mutation is associated with response to chemotherapy in colorectal liver metastases., The frequency of KRAS and BRAF mutations was low; KRAS mutations were detected in 1.6% and BRAF mutations in 4.7% of the biopsies for anal carcinoma., These findings support a model in which targeting MUC1-C inhibits mutant KRAS signaling in Non-small cell lung cancer cells and thereby reverses the epithelial-mesenchymal transition phenotype and decreases self-renewal., This study suggests that patients with mCRC with KRAS-mutated subclones (at least those with a KRAS-mutated subclones fraction lower or equal to 1%) had a benefit from anti-EGFR therapies., Differences in the KRAS mutational status during colorectal cancer disease progression., our study identifies coordinate hyperactivation of Notch1 and Ras/MAPK pathways as novel biomarkers for poor breast cancer outcome., None of the 66 tumors harbored mutations in KRAS exon 2, thus excluding KRAS mutations as a common event in squamous cell carcioma of the anogenital and head and neck region and as a cause of p16(INK4a) expression in these tumors., KRAS mutations are associated with pseudomyxoma peritonei., KRAS exon 2 mutations are independent predictors of shorter time to recurrence in patients with resected stage III distal colon cancers receiving adjuvant therapy, KRAS mutation in adenocarcinoma of the gastrointestinal type arising from a mature cystic teratoma of the ovary., KRAS mutations are associated with poor prognosis in Non-Small Cell Lung Cancer patients. Good diagnostic performance obtained from Malignant pleural effusion samples for detecting KRAS mutations., AKR1B10 is a unique enzyme involved in pancreatic carcinogenesis via modulation of the Kras-E-cadherin pathway., Mutated K-ras activates CDK8 to stimulate the epithelial-to-mesenchymal transition in pancreatic cancer in part via the Wnt/beta-catenin signaling pathway., These results suggest that the combination of a selective MEK inhibitor and a PI3K/mTOR inhibitor was effective in CRC harboring with KRAS and PIK3CA mutations., Report KRAS mutation status in colorectal neoplasms and neuroendocrine differentiation in primary/metastatic colorectal neoplasms., Our findings illuminate the mechanistic details of KRAS-mediated drug resistance and provide a preclinical rationale to improve the management of lung tumors harboring KRAS mutations with NRF2 pathway inhibitors., Binding of RAGE to oncogenic KRAS facilitates hypoxia-inducible factor 1 (HIF1)alpha activation and promotes pancreatic tumor growth under hypoxic conditions., KRas G12V has higher aggressiveness than KRas G13D in a colorectal cancer model, Although, the KRAS LCS6 is neither constitutional nor somatic biomarker for endometriosis, increased expression ratio of KRAS mRNA indicates its role in the implantation of endometrial tissue outside the uterine cavity., Mutant KRAS-induced expression of ICAM-1 in pancreatic acinar cells causes attraction of macrophages to expedite the formation of precancerous lesions., KRAS codon 13 mutations (in particular G13D) are associated with inferior survival in BRAF wild-type colorectal cancers in Chinese patients., This expert group recommends testing for KRAS and NRAS status in all patients with metastatic CRC being considered for anti-epidermal growth factor receptor (anti-EGFR) therapy, SMYD3-mediated methylation of MAP3K2 increases mutant K-Ras-induced activation of ERK1/2. (Review), scFv(CD44v6)-conjugated nanocarriers provide a highly efficient and safe platform for KRAS suppression in pancreatic cancer., KRAS gene mutations were detected 11 of 24 cases in exon 4 mutations., KRAS mutation is associated with metastatic lung adenocarcinomas., c-Met targeting enhances the effect of irradiation and chemical agents against malignant colon cells harboring a KRAS mutation., KRAS mutations occur in rare gastrointestinal stromal tumors with wild type KIT and PDGFRA., In this retrospective analysis, triplet chemotherapy with OCX was well tolerated and achieved encouraging efficacy in metastatic colorectal cancer irrespective of RAS/RAF mutation status., KRAS mutation is associated with refractory metastatic colorectal cancer, mutations are associated with decreased cancer-specific survival after lung stereotactic body radiation therapy for early-stage non-small-cell lung cancer, Mutated KRAS caused higher (18)F-FDG accumulation possibly by upregulation of GLUT1, Suppression of TET1-dependent DNA demethylation is critical for KRAS-mediated transformation., HER2 gene amplifications, and wild type KRAS genes are common in eyelid sebaceous carcinomas, miR-143 and miR-145 and the predicted target proteins API5, ERK5, K-RAS, and IRS-1 display regional differences in expression in the colon, Study sequenced a large clinical series of patients with metastatic colorectal cancer (mCRC) for RAS and PIK3CA mutations. RAS alterations occurred in 48% of mCRC cases, with mutations within KRAS exon 2 in 43%, KRAS exons 3 and 4 in 3%, and NRAS in 2% of cases. PIK3CA mutations occurred in about 10% of mCRC and were significantly associated with concurrent RAS mutation., KRAS mutations in both tumor tissue and plasma are a strong prognostic marker for poor outcomes in metastatic colorectal cancer., Data suggest that the status of p53 and KRAS may be considered for the targeted therapy against NF-kappaappa B in lung cancer patients., Mir206 targets ANXA2 and Kras genes in pancreatic adenocarcinoma., LRP6 phosphorylation by ERK1/2 may provide a unique point of convergence between KRAS/MAPK and Wnt/beta-catenin signalings during oncogenesis, Report low frequency of KRAS mutation in pancreatic ductal adenocarcinomas in Korean patients., Missense mutations were identified in the BRAF and KRAS genes in cutaneous melanoma cell line., IRS2 copy number gain, IGF-1R, IR-A, and IGFBP6 RNA expression levels, and KRAS and BRAF mutational status were identified as candidate predictive biomarkers for response to BMS-754807., activation of the RAS-mitogen-activated protein kinase pathway by BRAF and RAS mutations contributes significantly to the tumorigenesis of sporadic SCAP, Lung metastasis was more likely to develop during the disease course in patients whose tumour had a KRAS mutation than in those whose tumour did not have a KRAS mutation., K-Ras 4A expression was 2.7-fold higher in endometriosis than non-endometriosis eutopic samples; this overexpression mainly occurs through the proliferative phase of menstrual cycle, an MEK1/2 inhibitor potentiated the anti-tumor effects of cisplatin in KRAS-dependent lung cancer cells and an animal model through inhibition of BIM degradation., in different macroscopic subtypes of colorectal adenoma, KRAS mutation was noted more frequently in lateral spreading tumors than polypoid neoplasms; mutations in KRAS, BRAF or PIK3CA occurred in a mutually exclusive manner, Report mutations in SNP loci of K-RAS in neoplastic intestinal polyps and colorectal cancer., In unselected advanced non-small-cell lung cancer patients, KRAS mutations could be used as a potential negative predictor of clinical benefit from epidermal growth factor receptor tyrosine kinase inhibitors.[meta-analysis], Each mutation generates a distinct signature, with the most variability seen between G13D and the codon 12 KRAS mutants, KRAS codon 12 and 13 mutations are associated with pancreatic adenocarcinoma., high-resolution melt and allele-specific PCR could detect as low as 1.25% KRAS- or BRAF-mutant alleles., KRAS mutant allele-specific imbalance is a significant event in colorectal cancer, specifically associated with G13D mutation, and featuring a heterogeneous spatial distribution, that may have a role to predict the response to EGFR inhibitors., Results suggest that WT1 and c-MYC expression is important for survival in KRAS mutant tumors as opposed to KRAS wild-type non-small cell lung tumors., The KRAS(G12D) mutation identifies a subset of ampullary adenocarcinoma patients with poor prognoses and may be used to identify patients at risk of early recurrence and poorer survival who may benefit from adjuvant therapy., KRAS mutations are associated with response to chemotherapy in colorectal cancer., Addition of cetuximab to GEMOX chemotherapy improved progress-free survival in biliary tract neoplasms but this did not correlate with KRAS mutation status., KRAS and BRAF mutations are associated with inferior survival, independent of MSI status, in Japanese patients with curatively resected colorectal carcinoma., KRAS is a critical regulator for the metastatic behavior associated with mesenchymal features of breast cancer cells, implicating a novel therapeutic target for basal-type breast cancer., Latin American populations had a low frequency of KRAS mutations compared with European/North American populations., The frequencies of KRAS and IDHs mutations, which are associated with poor disease-free survival, were significantly higher in hepatitis-negative LCBs, KRAS gene mutation is associated with non small cell lung carcinoma., HPV presence was not associated with age, stage or grade of tumours, MSI or mutations in KRAS, TP53 or BRAF genes., miR-21 promotes malignant behaviors of colon cancer cells by regulating RASA1 expression via RAS pathways., Report high rates of KRAS mutations in Chinese colorectal carcinoma patients., KRAS mutations are associated with Metastatic Colorectal Cancer., Mutated KRAS and mutated BRAF seem to be prognostic factors in patients with Colorectal cancer who undergo lung metastasectomy., KRAS mutations portend a worse outcome with increased risk of recurrence in early-stage Non-small cell lung cancer and poorer survival in metastatic stage. It is associated with Adenocarcinoma subtype and smoking, and is common in Caucasian patients., KRAS amplification confers resistance to ROS1 targeting drugs in lung cancer., KRAS mutations were associated with stage IV lung adenocarcinoma adrenal metastases., RAS mutations cause vascular tumors including pyogenic granuloma, results suggest that KRAS mutation may be a useful prognostic marker for patients with metastatic colorectal cancer receiving mFOLFOX6 +/- bevacizumab therapy, especially for patients treated with mFOLFOX6 + bevacizumab, this is the first study focused on the effect of statins in selected patients with advanced-stage NSCLC harbouring KRAS mutation treated with EGFR-TKIs. A randomized prospective clinical trial should be conducted to confirm our results in the future., patients with KRAS mutations except for patients with KRAS codon 13 mutations that seem to be resistant to neoadjuvant CRT and less likely to achieve a pCR., MEKi induced the expression of negative regulators of mTORC1, including TSC1, TSC2 and Deptor, which occurred more significantly in BRaf-mutant cells than in KRas-mutant cells., The prognostic significance of KRAS gene mutations, evaluated by using two methods in patients with colorectal cancer, is reported., KRAS mutation is a poor prognostic factor in patients with metastatic colorectal cancer. In KRAS mutation metastatic colorectal cancer, mutation at codon 12 or at codon 13 had no relationship with prognosis., MEK1/2 inhibitor trametinib showed similar PFS and a response rate as docetaxel in patients with previously treated KRAS-mutant-positive non-small cell lung carcinoma., Neither all RAS gene mutation status nor PIK3CA mutation status was prognostic for PFS or OS., High MACC1 expression in combination with mutated KRAS G13 indicates poor survival of colorectal cancer patients, Based on our findings, we conclude that the hybcell-based compact sequencing technology represents a valuable alternative to the existing methods used for the detection of clinically relevant point mutations in the KRAS gene, KRAS mutation is associated with endometrial carcinomas and concomitant hyperplasia., Report KRAS mutation discordance between primary colorectal nsoplasms and their metastases., Review/Meta-analysis, In multivariable analyses, in both patients with EGFR-mutant and KRAS-mutant lung adenocarcinomas, advanced stage at the time of diagnosis was found to be independently associated with shorter survival., activated K-Ras regulation of brain neural stem cells proliferation requires Raf binding and suppression of retinoblastoma (Rb) function, KRAS(G12V)-transformed cells in transgenic zebrafish showed activation of the ERK-MAP kinase pathway and expressed the zebrafish homologue for human CXCL8, a cytokine produced by mammalian Ras-transformed cells in tumor-associated inflammatory lesions., Tumor mutant KRAS status is associated with an increased risk of venous thromboembolism in patients with metastatic colorectal cancer., miR-134 may function as a tumor suppressor in cell proliferation by targeting KRAS in renal cell carcinoma cells., gLCR has the capacity to detect one mutated allele in an excess of at least one million wild type alleles (0.0001 %) and is therefore an ideal technique for confirming doubtful KRAS mutation screening results obtained by other techniques, KRAS and EGFR co-mutation was detected in one case. PPMA patients with ALK rearrangements or KRAS mutation represent a unique subtype in Non-Small-Cell Lung Carcinoma, The frequency of mutations in either KRAS or PIK3CA were significantly higher in patients without lymph node metastasis than those with., the Eprobe system had a higher sensitivity for detecting KRAS mutations in colorectal cancer patient samples; these mutations could not be identified by Sanger sequencing, An inflammatory cue from oncogenic hepatocytes upon induction of kras(V12) expression causes a rapid recruitment of neutrophils to oncogenic liver and the neutrophils play a promoting role in early hepatocarcinogenesis., KRAS mutations were more prevalent in tubular-type than colloid-type intraductal papillary mucinous neoplasms-associated invasive carcinoma., KRAS mutations are usually present in the majority of metastatic colorectal cancer cells., FOLFOX adjuvant chemotherapy benefits patients with stage II or III colorectal cancer with KRAS mutant tumors and is worth further investigation, Study demonstrated the presence of recurrent GNAS and KRAS mutations in gastric foveolar metaplasia and gastric heterotopia lesions in the duodenum., The presence of a KRAS mutation in colon cancer patients increases the likelihood of disseminated disease., Among 264 patients, mutations in KRAS exon 2, KRAS exons 3 or 4, NRAS, BRAF and PIK3CA were detected in 34.1%, 3.8%, 4.2%, 5.4% and 6.4%, respectively. Thus, a total of 12.1% of patients without KRAS exon 2 mutations had other RAS mutations, Deacetylation of K-Ras by Sirt1 increased the transformation of Ras-GTP to Ras-GDP, promoting the activation of downstream of ERK1/2. In reverse, Ras/ERK pathway could also regulate Sirt1 transcription., Overexpression of mutant KRAS in Caco-2 cells led to an increase in CIP2A expression and cell proliferation., The data suggest a role for redox-dependent activation of wild-type KRAS through cysteine 118 in oncogenic HRAS-driven tumorigenesis., Results show that KRAS expression is downregulated by miR-193b that targets its 3'-UTR in pancreatic ductal adenocarcinoma and dysregulation of the miR-193b-KRAS axis appears to be involved in pancreatic carcinogenesis., ReviewMeta-analysis, Report EGFR expression/KRAS mutations and the effect of EGFR expression on stage, prognosis and response to conventional chemotherapy agents., KRAS mutations are associated with recurrence in hyperdiploid acute lymphoblastic leukemia., A high rate of homozygous and heterozygous mutations of codon 12, but not codon 13 and 61, may influence the invasive ductal carcinoma of breast risk in the South Indian population., Case Report, KRAS mutational status can be determined in biopsies representing bronchial pulmonary carcinomas because when a mutation is present it is generally present in all the histological patterns, The aim of this study was to evaluate the prognostic role of MMR status, BRAF mutations and specific KRAS point mutation in 762 patients in Chinese population, and several clinicopathologic features to better stratify colorectal cancer patients, CREB plays a key role in the K-RAS(V12)-mediated neoplastic phenotype and represents a suitable therapeutic target for murine and human K-RAS(V12)-induced tumors, EGFR and KRAS mutation were associated with non-small cell lung carcinoma., The effector-binding region of activated K-RAS4B is occluded by interaction with the membrane in one of the NMR-observable, and thus highly populated, conformational states., KRAS mutations and SEPT9 promoter methylation were present in 34% (29/85) and in 82% (70/85) of primary tumor tissue samples., Findings suggest that a high frequency of K-ras mutations occurs in Chinese metastatic colorectal cancer patients and that K-ras mutation is required to select patients for eligibility for cetuximab therapy., Studied the role of PAK1/Crk axis in transduction of the oncogenic KRAS signal in non-small cell lung cancer (NSCLC)., Estrogen withdrawal and a low estrogen state increase breast cancer risk in women with the KRAS-variant., Our results suggest that smoking is not a major cause of adenocarcinomas in situ. Rather, smoking may play a role in progression of adenocarcinomas in situ to invasive adenocarcinoma with AIS features, Determination of mutated KRAS seems to be of limited value in predicting long-term outcome in adenoma in the major duodenal papilla., The results suggest a possible association between KRAS mutations and mucinous differentiation in endometrial carcinogenesis, CYP1B1, KRAS and MTHFR variants are associated with shorter telomere length in postmenopausal women, KRAS activating mutation is relatively low in Korean colorectal cancer patients., KRAS mutation analysis may offer additional discriminatory power in separating benign microglandular hyperplasia from endometrial adenocarcinoma with microglandular pattern., ABL phosphorylates tyrosine 137 of H-, K-, and NRAS., The incidence of missense mutations in KRAS was much higher in patients with early treatment failure than in other groups, K-Ras stabilization by estrogen via PKCdelta has a role in endometrial tumorigenesis, PIK3CA amplification may be an early and important event in colorectal carcinogenesis and may drive the development of left-side tubular adenomas independently with KRAS mutation., miR-155 plays an important role in oncogenic K-Ras transformation mediated by cellular redox regulation, The K-ras mutational status of the primary colorectal cancer differed from that of the liver metastasis, and codon 13 mutations may explain such discrepancies., mTORC1/SREBP pathway is a major mechanism through which common oncogenic signaling events induce de novo lipid synthesis to promote aberrant growth and proliferation of cancer cells, Our results indicate that KRAS mutations are associated with inferior survival benefits for Non-Small Cell Lung Cancer but not for those treated with chemotherapies integrating cetuximab., Oncogenic KRAS sensitizes premalignant, but not malignant cells, to Noxa-dependent apoptosis through the activation of the MEK/ERK pathway., High mesothelin expression was strongly associated with mutant KRAS/wild-type EGFR and poor prognosis in advanced lung cancer., There is 20.3% KRAS discordance between primary and recurrent colorectal tumors, which is higher rate than is generally known., The structural data and measurements, obtained herein, indicate that measurable biochemical properties provide clues for identifying KRAS-driven tumors that preferentially signal through RAF., KRAS codon 12 mutations specifically G12V and G12S mutations were associated with worse prognosis after resection of colorectal liver metastasis especially among patients with recurrence after surgery., This study revealed that specific epidemiologic and clinicopathologic characteristics are associated with mismatch repair status stratified by KRAS mutation., In transgenic mice programmed to express both mutant oncogenes in the lung epithelium, the resulting tumors express either the KRAS, or the EGFR oncogene., Meta-analysis, K-Ras self-association can regulate effector binding and activity., cyclin D1 expression cooperates with KRAS and PTEN alterations in pathogenesis of NSCLC, and they could serve as potential multiple molecular markers for specific subgroups of NSCLC patients as well as prognostic markers for this type of cancer., EGFR and KRAS mutation status are both predictive factors for the treatment efficacy., Data suggest that detection of the c.34G>T KRAS transversion could imply biallelic germline mutY DNA glycosylase MUTYH mutation and lead to genetic counseling., KRAS Mutation is associated with recurrence in Colorectal Liver Metastases., Elevated calcium levels clinically observed in adenocarcinomas may explain calmodulin's involvement in recruiting and stimulating PI3Kalpha through interaction with its n/cSH2 domains as well as K-Ras4B; importantly, it also explains why K-Ras4B specifically is a key player in ductal carcinomas, such as pancreatic, colorectal, and lung cancers. [Review], LGALS9/galectin-9 induces fatal frustrated autophagy in KRAS mutant colon carcinoma that depends on elevated basal autophagic flux, BRAF, NRAS and KRAS gene mutations in plasma cell dyscrasias may have a role MEK-ERK pathway activation, Our data show that combined targeting of MEK and PI3K-AKT with mTOR is a better option than single agents alone for KRAS mutant NSCLC, thus opening the possibility of a beneficial treatment strategy in the future., Secondly, we show the molecular consequences of allele imbalance by deletion of either, a wild-type or a mutant allele in KRASG13D/WT CRC cells, Data show that RAS-MAPK pathway mutations may function as a biomarker for new therapeutic approaches to refractory disease., Tissue micro array availability, BRAF mutation and KRAS mutation were all independent prognostic factors for colorectal cancer survival., Report KRAS mutations/copy number variations and chromosome aberrations in colorectal adenocarcinomas., In patients with mutant KRAS codon 13, the mOS was not significantly different., In patients receiving selumetinib+docetaxel and harbouring KRAS G12C or G12V mutations there were trends towards greater improvement in overall survival, miR-10b was selectively increased in exosomes of cells with wild-type KRAS, while miR-100 was increased in exosomes of cells with mutant KRAS., (18)F-FDG PET/CT scans may be useful for predicting the KRAS status of metastatic CRC and help in determining the therapeutic strategies against metastatic CRC., Report a mutation spectrum that includes GNAS, KRAS and TP53 may be shared by mucinous neoplasms of the appendix., Colon cancers from Asians have a lower rate of KRAS mutations than blacks or whites., KRAS mutation status seems to identify two different subtypes of pancreatic ductal adenocarcinoma with similar outcome but distinct molecular features and probably different therapeutic targets., In SW48 cells, exon 2 mutations of the KRAS gene may influence antitumor effects of regorafenib., RAS mutations are associated with colorectal carcinoma., The results suggested that KRAS mutation could be associated with a reduced efficacy of chemoradiotherapy and a shortened survival time., KRAS mutations are associated with nonsmall-cell lung cancer., Patients with CRC and KRAS wt may derive greater survival benefit from (90)Y radioembolization therapy than patients with KRAS mutant., Mutations in KRAS exon 2 (codon 12/13) are an established predictor of lack of response to the anti-EGFR monoclonal antibodies cetuximab and panitumumab in patients with metastatic Colorectal cancer., The prevalence of oncogenic RAS mutations was higher among Arab Asian children than in other countries. RAS mutations in AML were found to coexist with other genetic aberrations, particularly MLL rearrangement, BCL-XL up-regulation by STAT3 contributes to mutant KRAS-mediated apoptosis resistance. Such resistance can be overcome by potent BIM induction and concurrent BCL-XL antagonism, KRAS mutation neither on primary tumor nor in circulating tumor cells was associated with clinical-pathological parameters in metastatic colorectal cancer., The KRAS mutation status does not influence the tumor response to the radiotherapy and survival in locally advanced rectal cancer patients who received preoperative chemoradiotherapy and curative surgery., These findings indicate that miR-143/145 rs4705343 and KRAS rs712 may contribute to the etiology of Cervical Squamous Cell Carcinoma in Chinese women., RAS-positive thyroid nodules, especially in older individuals, frequently demonstrate a benign phenotype.Cytologically benign nodules, even if RAS-positive, may be candidates for a non-operative observational strategy, Data show that small molecule protein kinase inhibitor DEL-22379 blocks proliferation of tumor cells harboring RAS-ERK pathway oncogenes., data suggest one-step screening platform for KIF5B-RET as well as EGFR, K-RAS, ALK oncogenic mutations be necessary for lung adenocarcinoma patients, Demonstrate a correlation between occurrence of DPYD gene variant c.496A>G and KRAS wild type status of colorectal cancer tissue., detection of somatic KRAS A146T and Q61H mutations in 2 out of 4 (50%) sarcomatoid Salivary duct carcinoma variants, is reported., Suggest common mutations of the KRAS gene can be used as an early determining marker for early diagnosis of prostate adenocarcinoma., KRAS and BRAF oncogenes have roles in colorectal cancer development and therapy resistance [review], KRAS 3'-UTR rs712 polymorphism interfered with has-let-7g/mRNA interaction, and showed that the minor allele was associated with an elevated risk for development of lung cancer in COPD., Studies indicate that KRAS and NRAS mutations are currently recognized as the best predictive factors for primary resistance to anti-EGFR monoclonal antibodies., KRAS mutations are frequent in our series of microsatellite instable cancers cases and are often found in a subpopulation of the tumour and not in the whole tumour, Data suggest that Src kinases inhibitors may act with different mechanisms in non-small cell lung cancer (NSCLC) depending on EGF receptor (EGFR)/Ras protein (Ras) mutational profile., KRAS/NRAS mutations are common in mesonephric carcinoma and are often accompanied by gain of 1q and mutations in chromatin remodeling genes, Case Report, anti-EGFR therapy is restricted to KRAS wild-type patients as it has been shown that KRAS exon 2-mutated patients do not respond to this therapy--{REVIEW}, combined pan-RAF and MEK inhibition can overcome intrinsic and acquired resistance to single-agent RAF/MEK inhibition, supporting dual pan-RAF and MEK inhibition as a novel therapeutic strategy for BRAF- and KRAS-mutant cancers, The significant association between mutated KRAS and tumor grade suggests that KRAS mutations may be involved in the formation of poorly differentiated clusters (PDC) of neoplastic cells in colorectal cancer, Results suggest a different pattern of sensitivity/resistance to cisplatin depending on the Kirsten Ras protein (KRAS) mutational status., NF2/merlin inactivation augments mutant RAS signaling by promoting YAP/TEAD-driven transcription of oncogenic and wild-type RAS, resulting in greater MAPK output and increased sensitivity to MEK inhibitors., In three cases of papillary carcinoma arising in struma ovarii (PSCS), novel BRAF and KRAS mutations were identified in two of three tumors suggesting that mutations in PCSO may differ from those commonly identified in papillary carcinoma of the eutopic thyroid., Risk of recurrence was significantly lower for non-KRAS G12V (HR, KRAS mutations are indicators of malignant transition in the progression to lung adenocarcinoma., BRAF and KRAS mutations show together a high prevalence in stage II and III MSI colon cancer and, when combined, are associated with poor survival compared to dWT cancers, which status confers an excellent cancer-specific survival., K-Ras mutation is associated with response to chemotherapy in metastatic colorectal cancer., let-7 is a tumor suppressor that negatively regulates RAS, also in Ewing Sarcoma, and HIF-1alpha may contribute to the aggressive metastatic behavior of Ewing Sarcoma, our studies suggest that Ras activation is a key determinant for dissemination and poor prognosis of ERalpha(+)/luminal breast cancer in humans, The KRAS gene may contribute to the formation of borderline mucinous cystadenoma., the presence of KRAS mutations has a mild negative impact on overall survival in advanced NSCLC patient treated with a first-line platinum-containing regimen, Colorectal cancer-related mutant KRAS alleles function as positive regulators of autophagy., Negative correlation between KRAS mutation and oncological outcome after resection of colorectal liver metastasis., KRAS gene mutations may have a prognostic role in colorectal cancer, KRAS Mutations are associated with Non-Small-Cell Lung Cancer., Data suggest that over-expression of lincRNA-p21 promotes up-regulation of p21 at both mRNA and protein levels in hepatic stellate cells; expression of lincRNA-p21 and p21 is down-regulated in cirrhotic liver patients as compared to normal subjects., RAS and BRAF wild-type status could help select an elderly and unfit population that could benefit from anti-epidermal growth factor receptor single agent therapy., GTP Binding and Oncogenic Mutations May Attenuate Hypervariable Region (HVR)-Catalytic Domain Interactions in Small GTPase K-Ras4B, Data show that RAS protein activation was the initiating oncogenic event, with polycomb repressive complex 2 (PRC2) subunits impairment being a secondary event., KRAS mutant lung adenocarcinomas appear to have a more intricate RAS linked signaling network than WT tumors., KRAS mutations are not associated with inferior progression-free and overall survival in advanced NSCLC patients treated with standard first-line platinum-based chemotherapy., Transfection of constitutively activated K-rasG12V in pancreatic cancer cells led to the transcriptional upregulation of MUC4 at the transcriptional level by AP-1, MAPK, JNK and NF-kappaB pathways and at the posttranscriptional level by RalB GTPase., The RAS/MAPK and PI3K/mTOR pathways are activated in the majority of cases of UPS. The RAS/MAPK pathway distinguishes a subgroup of patients with localized UPS with a worse outcome., EGFR and KRAS mutations were low in lung squamous cell carcinomas, and had no significant correlation with clinical features., KRAS mutant circulating free DNA was detected in patients with exocrine pancreatic cancer and associated with overall survival., Data indicate that KRAS protein mutation detection in archival tumour tissue showed no correlation to survival, whereas plasma KRAS status remained a strong predictive and prognostic factor., KRAS mutation may occur with MSI in colorectal cancers with wild-type BRAF. If a mutation in KRAS co-exists with MSI, then strong methylation of the MLH1 gene is unlikely, SLFN11 expression predicts good better survival in colorectal cancer patients with KRAS exon 2 wild type who have received oxaliplatin based adjuvant chemotherapy., Data indicate that tumors with proto-oncogene proteins BRAF or KRAS mutations were in correlation with elevated serum level of carbohydrate antigen (CA19-9) and carcinoma embryonic antigen (CEA)., Here we aimed to investigate the relationship between KRAS rs712 polymorphisms and hepatocellular carcinoma susceptibility, Vitamin C is selectively toxic to cells with mutant KRAS or BRAF alleles., Data show that Ras protein regulates inhibitor of growth protein 4 (ING4)-thymine-DNA glycosylase (TDG)-Fas protein axis to promote apoptosis resistance in pancreatic cancer., study concluded that 26% of patients had detectable FLT3-ITD or RAS mutation at transformation from myelodysplastic syndrome to acute myeloid leukemia, and these mutations were associated with very poor outcome, analysis of HRAS, KRAS and NRAS expression in colorectal tumor cells, Data show that tet methylcytosine dioxygenase 2 TET2, isocitrate dehydrogenases 1/2 IDH1/IDH2, serine/arginine-rich splicing factor 2 SRSF2, splicing factor 3b subunit 1 SF3B1, and ras proteins (KRAS/NRAS) are not conserved in dog mast Cell tumors., Ras.GDP weakly binds to the catalytic but not to the allosteric site of Sos., The TG/GG of KRAS-LCS (rs61764370) had a benefit from docetaxel treatment compared with the TT allele in terms of PFS., Overexpression of mTORC1 is associated with pancreatic cancer cells expressing mutant Ras., Data show that 11/105 patients failed all molecular analysis, In lung adenocarcinomas, EGFR mutation was higher in female and non-smoking patients, KRAS mutation only in patients with wild-type EGFR gene was higher., Study reports that oncogenic K-Ras, but not H-Ras, suppresses non-canonical Wnt/Ca(2+) signaling, an effect that contributes strongly to its tumorigenic properties., Using the extensive guanine-rich region of the kRAS core promoter, and particularly the G4mid structure, future drug discovery programs will have potential to develop a potent, specifically targeted small molecule to be used in the treatment of cancers, PIK3CA mutations were observed in 32% (8) of the 25 breast cancer tissues examined, Sequencing of exon 2 of KRAS suggested that 20% (5) of the 25 samples harbored a mutation and 16% (4) of BRAF harbored a mutation., use of sorafenib has been ineffective in the management of advanced Colorectal cancer (CRC) patients with KRAS mutation, combination of selective BRAF inhibitors plus EGFR inhibitors may represent a good therapeutic strategy in BRAF-mutant CRC., mEGFR are associated with higher response rate (RR) to brain metastasis radiotherapy than wild-type EGFR/RAS or mKRAS., Kras single nucleotide polymorphisms rs12228277 and rs61761074 of intron 2 result in differential binding patterns of lung nuclear proteins.Rs61761074 demonstrated a significant correlation with allele frequency in non-small-cell lung cancer., our study suggested that black rice anthocyanins extract suppress metastasis in breast cancer cells by targeting the RAS/RAF/MAPK pathway, As depicted in Figure 3, APC (25%) followed by KRAS (20%), TP53 (14%), and PIK3CA (11%) were the most frequently mutated genes., As an example of the application of this platform we performed the analysis of six common mutations in the codon 12 of KRAS gene (G12A, G12C, G12D, G12R, G12S, and G12V)., KRAS promoter oligonucleotide with decoy activity dimerizes into a unique topology consisting of two G-quadruplex units.Nucleotides of the MAZ binding G-rich motif are dynamic and could be available for sequence or structure based recognition, miR-31 directly targets and reduces expression of negative regulators of RAS/MAPK signaling, this study was unable to confirm that KRAS-driven tumor lines require macroautophagy for growth., We observed no statistically significant association between BC risk and the let-7a KRAS rs712 polymorphism, These results indicate that CREG1 is a down-stream effector of KRAS in a sub-type of non-small cell lung cancer cells and a novel candidate biomarker or therapeutic target for KRAS mutant non-small cell lung cancer., The HSP90 inhibitor, NVP-AUY922, sensitizes KRAS-mutant non-small cell lung cancer with intrinsic resistance to MEK inhibitor, trametinib., Data show that microRNA miR-365 could inhibit the proliferation and promote the apoptosis in SOSP-9607 osteosarcoma cells probably by mediating the expression of KRAS protein., In operated pancreatic adenocarcinoma, incidence of mutations was, Modulation of Polycomb repressive complexes by either Ezh2 overexpression or Eed deletion enhances KRAS-driven adenomagenesis and inflammation, As a consequence, Slug transcription is down-regulated relieving A549 cells from Slug-mediated repression of E-cadherin transcription, thereby diminishing the metastatic potential of these oncogenic Ras-expressing NSCLC cells, Meta-analysis, KRAS and PIK3CA mutations can influence the response of DLD1 colorectal cancer cell lines to MEK and PI3K inhibitors, but that the effect is dependent on the experimental model used to assess drug sensitivity., MUC1 expression significantly correlated with that of MYC and its target genes in human KRAS mutant NSCLC tumors., Aurora kinases are important KRAS targets in lung cancer., Confirm contribution of PTPRZ1, and especially PTPRQ, in CRC carcinogenesis and demonstrated that PTPRQ expression is correlated with KRAS mutation., miR-1 was suppressed by LMP1 and its tumour-suppressive effects were mediated chiefly by repressing K-ras expression in nasopharyngeal carcinoma., Kras insertion mutations cause reduced intrinsic GTP hydrolysis rates, protein accumulation in the GTP-bound conformation and resistance to GAP-mediated GTP hydrolysis. Kras with switch 2 insertions are impaired for PI3 kinase binding and Akt activation., Data suggest bisphenol S binds to K-Ras4B binding pocket previously identified as binding site for various low molecular weight compounds including bisphenol A (another plasticizer/endocrine disruptor)., A high molecular and genetic concordance between primary tumor (PR) and PDX was confirmed by the evaluation of biliary epithelial markers, tissue architecture, genetic aberrations (including K-RAS G12D mutation), and transcriptomic and microRNA profiles, CDK1 is a synthetic lethal target for KRAS mutant tumors., The combination of tivantinib and CETIRI was well tolerated but did not significantly improve PFS in previously treated KRAS WT metastatic colorectal cancer, the RAS mutation in lymphoid cells is tightly linked with various autoimmune symptoms. The presence of the RAS mutation in lymphocytes should be reconsidered as a pathogenesis in cases of autoimmunity., The therapeutic potential of PKCiota-ELF3-NOTCH3 signal inhibition to more effectively treat KRAS LADC., Low incidence of KRAS mutations in adenocarcinomas of the ampulla of Vater suggest no major role in tumorigenesis., KRAS mutations are more common in females and smokers, but are not associated with chronic obstructive pulmonary disease status in non-small cell lung cancer patients., KRAS Mutation is associated with response to therapy in Rectal Cancer., The KRAS mutated Colorectal Cancers have less aggressive phenotype in comparison to the BRAF-mutated Colorectal Cancers., conclude that from the point of view of practical KRAS mutation testing for predictive purposes in patients with colorectal cancer,
OFFICIAL_GENE_SYMBOL kras,
OMIM_DISEASE Bladder cancer, somatic, Breast cancer, somatic, Gastric cancer, somatic, Schimmelpenning-Feuerstein-Mims syndrome, somatic mosaic, Lung cancer, somatic, Pancreatic carcinoma, somatic, Leukemia, acute myeloid, Noonan syndrome 3, RAS-associated autoimmune leukoproliferative disorder, Cardiofaciocutaneous syndrome 2,
SP_COMMENT alternative products:Isoforms differ in the C-terminal region which is encoded by two alternative exons (IVA and IVB), disease:Defects in KRAS are a cause of acute myelogenous leukemia (AML) [MIM:601626]. AML is a malignant disease in which hematopoietic precursors are arrested in an early stage of development., disease:Defects in KRAS are a cause of cardiofaciocutaneous syndrome (CFC syndrome) [MIM:115150]; also known as cardio-facio-cutaneous syndrome. CFC syndrome is characterized by a distinctive facial appearance, heart defects and mental retardation. Heart defects include pulmonic stenosis, atrial septal defects and hypertrophic cardiomyopathy. Some affected individuals present with ectodermal abnormalities such as sparse, friable hair, hyperkeratotic skin lesions and a generalized ichthyosis-like condition. Typical facial features are similar to Noonan syndrome. They include high forehead with bitemporal constriction, hypoplastic supraorbital ridges, downslanting palpebral fissures, a depressed nasal bridge, and posteriorly angulated ears with prominent helices. The inheritance of CFC syndrome is autosomal dominant., disease:Defects in KRAS are a cause of juvenile myelomonocytic leukemia (JMML) [MIM:607785]. JMML is a pediatric myelodysplastic syndrome that constitutes approximately 30% of childhood cases of myelodysplastic syndrome (MDS) and 2% of leukemia. It is characterized by leukocytosis with tissue infiltration and in vitro hypersensitivity of myeloid progenitors to granulocyte-macrophage colony stimulating factor., disease:Defects in KRAS are the cause of Noonan syndrome 3 (NS3) [MIM:609942]. Noonan syndrome (NS) [MIM:163950] is a disorder characterized by dysmorphic facial features, short stature, hypertelorism, cardiac anomalies, deafness, motor delay, and a bleeding diathesis. It is a genetically heterogeneous and relatively common syndrome, with an estimated incidence of 1 in 1000-2500 live births. Rarely, NS is associated with juvenile myelomonocytic leukemia (JMML). NS3 inheritance is autosomal dominant., disease:KRAS mutations are involved in cancer development., enzyme regulation:Alternate between an inactive form bound to GDP and an active form bound to GTP. Activated by a guanine nucleotide-exchange factor (GEF) and inactivated by a GTPase-activating protein (GAP)., function:Ras proteins bind GDP/GTP and possess intrinsic GTPase activity., online information:The Singapore human mutation and polymorphism database, similarity:Belongs to the small GTPase superfamily. Ras family., subunit:Interacts with PHLPP.,
muscle RAS oncogene homolog(MRAS) muscle RAS oncogene homolog(MRAS) Related Genes Homo sapiens
CHROMOSOME 3,
CYTOBAND 3q22.3,
ENSEMBL_GENE_ID ENSG00000158186,
GENERIF_SUMMARY implicated in a novel pathway of neuronal differentiation by coupling specific trophic factors to the MAPK cascade through the activation of B-Raf, These findings proved a crucial role of the cross-talk between two Ras-family GTPases M-Ras and Rap1, mediated by RA-GEF-2, in adhesion signaling., Identification of one new CAD risk locus on 3q22.3 in MRAS, and suggestive association with a locus on 12q24.31 near HNF1A-C12orf43., Both MRAS and SHOC2 play a key role in polarized migration., The MRAS gene loci might have a minor effect in conferring susceptibility to coronary artery disease in the Chinese population., The association of the MARS rs6782181 polymorphism and serum lipid levels is different between the Mulao and Han populations, or between males and females in the both ethnic groups.,
OFFICIAL_GENE_SYMBOL MRAS,
SP_COMMENT function:May serve as an important signal transducer for a novel upstream stimuli in controlling cell proliferation. Weakly activates the MAP kinase pathway., induction:By interleukin-9, but not by IL-2 or IL-4., similarity:Belongs to the small GTPase superfamily. Ras family., subunit:Interacts with RGL3., tissue specificity:Expression highly restricted to the brain and heart.,
neuroblastoma RAS viral oncogene homolog(NRAS) neuroblastoma RAS viral oncogene homolog(NRAS) Related Genes Homo sapiens
CHROMOSOME 1,
CYTOBAND 11p15.5, 1p13.2,
ENSEMBL_GENE_ID ENSG00000213281,
GENERIF_SUMMARY Mutations were detected by using allele-specific amplification method., BMECs co-expressing SV40T, hTERT and N-ras exhibited an overtly transformed phenotype; forming very large colonies with an altered morphology and generating rapidly growing tumours in vivo., Regulation of Fas-mediated apoptosis by N-ras in melanoma., Protein kinase C mediates mutant N-Ras-induced developmental abnormalities erythropoiesis, giving rise to phenotypic and functional abnormalities commonly observed in preleukemia., role of interleukin-6 in activation of expression, HDL induced a potent signal through a Ras/MAPK pathway mediated by a pertussis toxin-sensitive G-protein coupled receptor to the angiogenic phenotype in HCECs., high frequency of NRAS codon 61 mutations detected in primary hereditary melanomas may be the result of a hypermutability phenotype associated with a hereditary predisposition for melanoma development in patients with germline CDKN2A mutations, NRAS and BRAF mutations arise early during melanoma pathogenesis and are preserved throughout tumor progression, Acquisition of N-ras mutation is frequently associated with progression of myelodysplastic syndrome to acute myeloid leukemia, Mutations in N-ras gene is associated with malignant melanomas, Data show that Golgi-associated N-Ras is the critical Ras isoform and intracellular pool for low-grade T cell receptor signaling in Jurkat T cells., Low frequency of NRAS and KRAS2 gene mutations in childhood myelodysplastic syndromes., NRAS mutations are frequent in acute myeloblastic leukemia with normal karyotype., oncogenic NRAS is important for avoidance of apoptosis in melanomas that harbor the codon 61 NRAS mutation, Although BRAF and NRAS mutations are likely to be important for the initiation and maintenance of some melanomas, other factors might be more significant for proliferation and prognosis in subgroups of aggressive melanoma, Overactivation of N-Ras61K induces cytoplasmic mislocalization of p27 and disrupts TGF-beta-mediated Smad nuclear translocation by activation of the Mek/Erk pathway., Ras mutations do not play a significant role in the pathogenesis of multiple myeloma in the Spanish population, NRAS and BRAF activating mutations can coexist in the same melanoma, but are mutually exclusive at the single-cell level, In 239 Thai adult AML cases, 35 RAS mutations were found in 32 cases (13%) predominantly classified as M1/M2 (53%) followed by M4/M5 (38%). Ten cases were positive for NRAS codon 12, 11 for NRAS codon 61, 13 for NRAS codon 13, and one for KRAS codon 13., ras may be involved in early stages of larynx carcinogenesis and may be activated by other mechanisms different from mutations, such as epigenetic events, NRAS mutation is associated with melanoma and melanocytic nevi., The chemical properties and stucture of the membrane bound C-terminus of N-ras is reported., Ras gene mutations, mostly involving the N-Ras gene, were detected in 20% of the multiple myeloma patients; Ras gene mutations are not likely to represent a master lesion in MM, NRAS mutations were associated with a significantly higher Clark level of invasion in melanoma tumours, Our data suggest that the activity of specific RAS isoforms is context-dependent and provide a possible explanation for the prevalence of NRAS mutations in melanoma., patients having juvenile myelomonocytic leukemia with NRAS or KRAS2 glycine to serine substitution received no chemotherapy, but hematologic improvement was observed during a 2- to 4-year follow up, data indicate that both early-life UV exposure and nevus propensity contribute to occurrence of BRAF+ melanoma, whereas nevus propensity and later-life sun exposure influence the occurrence of NRAS+ melanoma, observations on the effects of NRAS activation indicate that RAS-inactivating drugs, such as farnesyltransferase inhibitors should be examined in human autoimmune and lymphocyte homeostasis disorders, Nras gene mutation might be one of the mechanisms of oncogenesis of lung adenocarcinoma., No mutations in NRAS was found in pilocytic astrocytomas., Ras mutations were found in 33% of the papillary thyroid carcinomas, CD155, at least in part, enhances the proliferation of ras-mutated cells, expression of RET, nuclearRAS, and ERK proteins is greatly enhanced in papillary thyroid carcinoma cells and Hashimoto's thyroiditis oxyphil cells., Frequently mutated in high hyperdiploid childhood acute lymphoblastic leukemia., Data indicate that a critical component of Ras signaling is the activation of PLD., 54% of childhood CBF-AML had RTKs and/or Ras mutations, 16k PRL inhibits cell migration by blocking the Ras-Tiam1-Rac1-Pak1 signaling pathway in endothelial cells, mutation of N-RAS or B-RAF, signature genetic lesions present in most MMs, potently induced the expression of cell-surface CD200, a repressor of DC function., NRAS mutation is not associated with cutaneous melanoma, N-ras mutation is associated with familial non-medullary thyroid carcinoma, restricting CDC25A can limit tumorigenesis induced by the HER2/neu-RAS oncogenic pathway without compromising normal cell division or viability [review], the Ras-Net (Elk-3) pathway involves microtubules and is inhibited by pyrazoles, Mitogen-activated protein kinase (MAPK) activity is subject to regulation even in BRAF/NRAS mutant melanoma cells and that high MAPK pathway signaling may be important only in distinct subsets of tumor cells., NRAS mutation is associated with disease stabilization in melanoma, AML patients carrying mutRAS benefit from higher cytarabine doses more than wtRAS patients. This seems to be the first example of an activating oncogene mutation favorably modifying response to higher drug doses in AML., Silencing of N-Ras gene expression using shRNA decreases transformation efficiency and tumor growth in transformed cells induced by anti-BPDE., co-overexpression of KIT/CDK4 is a potential mechanism of oncogenic transformation in some BRAF/NRAS wild-type melanomas, analysis of a signaling mechanism for the regulation of the Ras/ERK pathway based on the eNOS-dependent differential activation of N-Ras and K-Ras at specific cell compartments, N-RAS(Q61K) and B-RAF(V600E) contribute to melanoma's resistance to apoptosis in part by downregulating Bim expression, Mutation in NRAS is associated with childhood acute lymphoblastic leukemia, Stimulation of human mast cells by activated T cells leads to N-Ras activation through Ras guanine nucleotide releasing protein 1., suppression of oncogenic NRAS by siRNA can induce growth arrest and inhibit invasion of human melanoma cells by modulating the levels of these gene products, No NRAS1 mutations were observed in both the melanocytic aggregate and the melanoma, NRAS and BRAF mutations increase from the radial to the vertical growth phase in cutaneous melanoma, failed to find nRAS mutations in bladder tumor samples, Mutation in NRAS is associated with adrenocortical carcinomas., The present study indicates that esophageal neoplasms have a high frequency of NRAS mutations unlike mucosal neoplasms of other sites., REVIEW summarizes the literature on NRAS and BRAF activating mutations in melanoma tumors with respect to available data on histogenetic classification as well as body site and presumed UV-exposure., Targeting NRAS alone or both BRAF and CRAF in combination or both BRAF and PIK3CA together showed delay in tumor growth., Characterization of candidate gene copy number alterations in the 11q13 region along with BRAF and NRAS mutations in human melanoma., Transformation with N-RAS proved to increase the leading edge proportion and to considerably redistribute pseudopodial activity along the cell edge., analysis of the effect on the Ras/Raf signaling pathway of post-translational modifications of neurofibromin, analysis of coexisting NRAS and BRAF mutations in primary familial melanomas with specific CDKN2A germline alterations, NRAS mutations affect tumor necrosis factor-induced apoptosis in colon carcinoma cells via ERK-modulatory negative and positive feedback circuits along with non-ERK pathway effects, Data show that in hypoxic conditions or coexpressed with a constitutively active form of HIF-1alpha, c-Kit mutants activate the Ras/Raf/Mek/Erk pathway, stimulate proliferation and transform melanocytes., Backbone conformational flexibility of the lipid modified membrane anchor of the human N-Ras protein investigated by solid-state NMR and molecular dynamics simulation., RAS and CSF3R mutations in severe congenital neutropenia., assessment of NRAS mutations in juvenile myelomonocytic leukaemia, Although oncogenic NRAS expression alone was found to be insufficient to promote tumor formation, loss of functional p53 was found to collaborate with NRAS expression in the genesis of melanoma., study reports that germline NRAS mutations conferring enhanced stimulus-dependent MAPK activation account for some cases of Noonan syndrome; findings provide evidence for an obligate dependency on proper NRAS function in human development and growth, Screening for BRAF, RET, KRAS, NRAS, and HRAS mutations, as well as RET-PTC1 and RET-PTC3 rearrangements, was performed on cases of Hashimoto thyroiditis with a dominant nodule, Formalin-fixed primary melanomas from relapsed and nonrelapsed patients were sequenced for common BRAF and NRAS mutations. BRAF/NRAS mutations were detected in 77% of relapsers and 58% of nonrelapsers and did not predict ulceration or mitotic rate., whereas H-Ras and N-Ras were unable to localize to the plasma membrane in the presence of USP17, K-Ras4b localization was unaffected, Significant K-ras mutations were frequently detected in the major duodenal papilla and gastric and colonic mucosa of autoimmune pancreatitis patients, Specific point mutations of activated N-ras were detected in 9% (5 of 55) of the bladder cancer patients, all being missense., NRAS mutations are associated with relapsed childhood high hyperdiploid acute lymphoblastic leukemia., NRAS mutations contribute to evolution of chronic myelomonocytic leukemia to the proliferative variant., Ras induces ARC in epithelial cancers, and ARC plays a role in the oncogenic actions of Ras, if KRAS is not mutated, assessing BRAF, NRAS, and PIK3CA exon 20 mutations (in that order) gives additional information about the efficacy of cetuximab plus chemotherapy in metastatic colorectal cancer., experiments further confirmed the link between the loss of neurofibromin and increased activity of Ras/MAP kinase pathways and the activation of downstream transcriptional mechanisms in MPNSTs from NF1 patients, p16(INK4A) promoter methylation in melanoma was significantly overrepresented in NRAS-mutated samples compared to NRAS wild-type samples (P=0.0004), indicating an association between these two events, Endogenous Ras activation occurs only at the plasma membrane of live Jurkat T lymphocytes; all signals transmitted via the T cell receptor/Ras pathway originate at the T cell surface., association between MC1 receptor germline variation and BRAF/NRAS mutations in melanoma, the frequency and spectrum of N-RAS gene mutation differ between biologically distinct subtypes of AML but do not significantly influence prognosis and clinical outcome in patients with AML., NRAS mutations were detected in 5 (2.2%) of the 225 colorectal cancers and tended to occur in left-sided cancers arising in women, but did not seem to be associated with any of the molecular features that were examined., Yiqi Yangyin Recipe can inhibit the colonic proliferation of AML cells, and decrease the expressions of FLT3 and N-ras., melanomas escape B-RAF(V600E) targeting not through secondary B-RAF(V600E) mutations but via receptor tyrosine kinase (RTK)-mediated activation of alternative survival pathway(s) or activated RAS-mediated reactivation of the MAPK pathway, Primary esophageal melanomas of Caucasian patients did not harbor mutations of NRAS., Activating mutations, specifically in NRAS, are found exclusively in advanced forms of systemic mastocytosis and may precede the proto-oncogene protein c-kit D816V mutation in clonal development., NRAS mutation was frequently evident in patients with nodular melanoma (OR=1.894; P<0.001) and in melanomas arising in chronic sun-damaged skin (OR=1.887; P=0.018)., Mutations in PIK3CA, KRAS and NRAS were exclusive to tumors of uterine origin and age-adjusted Cox proportional hazards modeling associated advanced age, stage and TP53 mutations with decreased survival in the uterine subset., N-Ras(G12D) induces features of stepwise transformation in preleukemic umbilical cord blood cultures expressing the AML1-ETO fusion gene., study analyzed 90 samples of cutaneous T-cell lymphomas patients and found 2 KRAS (G13D) and 2 NRAS (Q61K) mutations, Mutations in NRAS from individuals with Noonan syndrome activated N-Ras signaling and induced developmental defects in zebrafish embryos., Alterations of the NRAS gene is associated with myelodysplastic syndromes and acute myeloid leukemia., 26 of colorectal tumors were mutant for NRAS., NRASmut did not affect the outcome in pediatric acute myeloid leukemia, The NRAS codon 61 mutation in giant congenit-al melanocytic nevi was significantly related to the amount of sun exposure., The tumor transformation potential of endogenous oncogenic Nras is both dose- and cell type-dependent., The study demonstrated that activated NRAS played an important part for delNS1 H5N1 virus replication in MDCK cells., NRAS mutations were associated with thicker tumors and higher rates of mitosis when compared to BRAF(V600E) and wild type melanoma., The low frequency of NRAS and BRAF mutations indicate that these genes are not common, but probable events in oral mucosal melanoma pathogenesis., Cholangiocyte N-Ras protein mediates lipopolysaccharide-induced interleukin 6 secretion and proliferation, Patients with mutations in BRAF or NRAS gene are frequently present with ulceration, and mutation in BRAF or NRAS gene is indicator for poor prognosis., N-RAS Q61R mutation was detected in 6% of tumours, 3% of classic papillary thyroid carcinoma and 10% of follicular variant papillary thyroid carcinoma., Wild type N-ras appears to mediate its anti-malignant effect by downregulating decorin expression., analysis of N-Myc and c-Myc synthesis, degradation, and transcriptional activity by the Ras/mitogen-activated protein kinase pathway, c-Met is more likely to be activated in both NRAS-mutated and wt/wt melanomas; melanoma cells with these genotypes, particularly NRAS mutants, are more sensitive to pharmacologic c-Met inhibition, Activated human N-ras v12 can play a role in murine B- and plasma cell homeostasis & that activated N-Ras & c-Myc can cooperate to induce B-cell neoplasia., correlation of mutations with clinical response to high-dose IL-2 in patients with advanced melanoma, NRAS mutation status was identified as an independent predictor of shorter survival after a diagnosis of stage IV melanoma., RET mutations may have a role in medullary thyroid carcinoma, while BRAF, AKT1, and CTNNB1 do not; the role of HRAS, KRAS, and NRAS mutations are not determined, KRAS mutations to be more frequent than NRAS mutations in pediatric patients with acute myeloid leukemia., Investigation the prevalence of mutations in the NRAS gene and its correlation with demographic characteristics, tumor location and stage in 100 colorectal carcinoma patients from India., Report marked differences in the genetic pattern of the BRAF or NRAS mutated and wild-type melanoma subgroups., study examined the mutational spectra of Ras isoforms curated from large-scale tumor profiling and found that each isoform exhibits surprisingly distinctive codon mutation and amino-acid substitution biases, BRAF/NRAS mutations were identified in 58% of primary melanomas, Thyroid follicular carcinomas harbored RAS mutations, and the mutation was predominantly found in the NRAS codon 61 (22/33, 67%)., study reports 2 patients with somatic mosaicism for oncogenic NRAS mutations (G12D and G12S) associated with the development of juvenile myelomonocytic leukemia, In primary melanocytic tumours of the CNS, GNA11 and N-RAS mutations represent a mechanism of MAPK pathway activation alternative to the common GNAQ mutations, Lung cancers with acquired resistance to EGFR inhibitors occasionally harbor BRAF gene mutations but lack mutations in KRAS, NRAS, or MEK1., As has been reported in other common types of melanoma, V600 BRAF mutation is the most common mutation of those tested in spindle cell melanoma. NRAS or KIT mutation appears to be rare, if not completely absent., oioiuh ohhiu iuhli u hliuh liuh iluh, NRAS germline mutations are a rare cause of Noonan syndrome or juvenile myelomonocytic leukemia., Data indicate that mutation frequency in malanoma patients was found witih BRAF(V600) in 51%, NRAS in 19%, PI3K pathway in 41% and PTEN in 22%., GAB2 is a novel regulator of tumor angiogenesis in NRAS-driven melanoma, We conclude that the presence of BRAF mutation, NRAS mutation, and the absence of an immune-related expressed gene profile predict poor outcome in melanoma patients with macroscopic stage III disease., N-ras expression was not associated with pathogenesis and biological behavior of thymic epithelial neoplasms., findings suggest a gradient model of oncogenic NRAS signaling in which the output is gated, resulting in the decoupling of discrete downstream biological phenotypes as a result of incomplete inhibition., identified a single activating mutation in NRAS and complete absence of oncogenic mutations in all other genes tested in aggressive pediatric rhabdoid tumors, The cAMP pathway is more frequently impaired in melanoma than could be predicted by the MC1R or NRAS genotype., SHOC2 and CRAF mediate ERK1/2 reactivation in mutant NRAS-mediated resistance to RAF inhibitor., We found that NRAS-mutant melanomas were significantly more likely from older patients and BRAF-mutant melanomas were more frequent in melanomas from the trunk., Localization of the NRAS, MiR-145 suppressed AKT and ERK1/2 pathways and HIF-1 and VEGF expression by targeting N-RAS and IRS1, miR-148b controls malignancy by coordinating a novel pathway involving over 130 genes and, in particular, it directly targets players of the integrin signaling, such as ITGA5, ROCK1, PIK3CA/p110alpha, and NRAS, as well as CSF1, The prevalence of RAS mutations in the present series of medullary thyroid cancer (MTC) was 10.1%, and 17.6% when considering only RET-negative cases. RAS mutations were found in MTC tumor tissue but not in peripheral blood indicating their somatic origin, Cooperation between p53 and v-Ras control critical genes related to tumorigenesis.{review], Primary melanoma of the CNS in children is driven by congenital expression of oncogenic NRAS in melanocytes, mutational status of N-RAS and K-RAS genes in a cohort of 504 Chinese acute myeloid leukemia patients; mutation frequency of N-RAS and K-RAS were 9.7 percent and 2.9 percent respectively; concluded RAS mutations are associated with some biologically specific subtypes of AML but don't impact clinical outcome in Chinese patients, mutations in N-RAS may play a role in acral lentiginous melanomas, These results suggest that single postzygotic NRAS mutations are responsible for multiple congenital melanocytic nevi and associated neurological lesions in the majority of cases., study demonstrated that RAS mutations frequently occur in Mixed Lineage Leukemia (MLL)-rearranged infant acute lymphoblastic leukemia (ALL) cases and especially in t(4;11)-positive infant ALL patients and their presence represents an independent poor prognostic factor, Gene expression changes due to neurofibromin modulation but independent of NRAS and MEK1/2 regulation in malignant peripheral nerve sheath tumor cells indicated bone morphogenetic protein 2 (Bmp2) signaling as a key pathway., A significant proportion of fast-growing melanomas bear mutations in NRAS., Data suggest that mutations in NRAS are relatively common (7/28 patients, 25%, p.Gln61Arg) in subjects with partially-encapsulated or well-circumscribed follicular variant of papillary thyroid carcinoma in Boston area., Wild-type copies of HRas, NRas and KRas play unique roles in the context of mutant KRas-driven tumours., NRAS mutations define a distinct subset of lung cancers with potential sensitivity to MEK inhibitors., findings implicate the HMGA2-IGFBP2-NRAS signaling pathway as a critical oncogenic driver in embryonic rhabdomyosarcoma, these studies have identified Wee1 as a key target of XL888, suggesting novel therapeutic strategies for NRAS-mutant melanoma., The presence of NRAS or BRAF mutations in a mutually exclusive pattern in roughly half (47%) of conjunctival melanomas and the pattern of CNAs argue for conjunctival melanoma being closely related to cutaneous and mucosal melanoma, NRAS or KIT mutations and cyclin D1 amplification can be found in a proportion of primary melanomas of the sinonasal tract., We observed 3 cases with N-ras mutations in codon 12 (3.6%), 2 cases in codon 13 (2.4%), and 1 case in codon 61 (1.2%)., low BRAF as well as NRAS expression levels were associated with a longer progression-free survival in the total population, Nras(G12D/+) mutation promotes leukemogenesis., NRAS mutations are associated with myelodysplastic syndromes., The frequency of NRAS mutations is lower in the Asian population than in Caucasian patients with primary and metastatic melanomas., Data suggest that NRAS activation occurs at the plasma membrane and suggest that depalmitoylation, and thereby removal of NRAS from the plasma membrane, contributes to down-regulation of signal transduction involving Ras proteins., We found that inherited variants od CDKN2A have no effect of ther prevalence of BRAF/NRAS mutations in melanoma., NRAS mutation is associated with myelodysplastic syndromes and acute myeloid leukemia., BRAF, NRAS, and c-Kit molecular analyses among patients affected by nail apparatus melanoma were investigated., Co-amplification of these candidate genes or the CCND1 amplification along with either BRAF or NRAS mutations might be more important for prognosis than the presence of these alterations alone., This study investigated the impact of KRAS, NRAS, BRAF, PI3KCA and TP53 status on outcome of elderly metastatic colorectal cancer patients, Melanomas arising in SSD skin have higher mutation loads and contain a spectrum of molecular subtypes compared with BRAF- and NRAS-mutant tumors indicating multigene screening approaches, The study found a high concordance of NRAS mutation status between paired metastases diagnosed at different time points., Findings show that KIT and BRAF mutations are only rarely present in SNMMs, whereas NRAS mutations seem to be relatively more frequent., the presence of a BRAF- or NRAS mutation in a nevus was not associated with the risk of malignant transformation., Comparison of 136 melanoma patients with NRAS exon 1 (18%) and exon 2 (82%) mutations found an association with primary tumor histology (P = .0096) only., Prevalence and distribution of pathogenetic mutations in BRAF and NRAS genes were evaluated in multiple melanoma lesions from patients with different geographical origin within the same Italian population., mutation in acral lentiginous melanoma of Swedish patients, Finding of somatic activating HRAS and NRAS mutation in bone, the endogenous source of FGF23, provides the first evidence that elevated serum FGF23 levels, hypophosphatemia and osteomalacia are associated with pathologic Ras activation., mutations in KRAS codon 61, KRAS codon 146, BRAF, NRAS, or PIK3CA detected in Asian patients were not predictive of clinical benefits from cetuximab treatment., KRAS/NRAS mutation predicts early lung recurrence and worse survival after curative resection of colorectal liver metastases., RAS mutations predict a lack of response to anti-EGFR therapy in patients with metastatic colorectal cancer., NRAS mutations were associated with poorer overall survival of patients with pediatric B cell precursor acute lymphoblastic leukemia., analysis of the NRAS mutation, which is the sole recurrent somatic mutation in large congenital melanocytic nevi, Report role of NRAS oncogenetic risk classification in the prognosis of adult T-cell acute lymphoblastic leukemia., Study suggests TRIM33 and NRAS-CSDE1 as candidate genes for autism, and may provide a novel insight into the etiology of autism, NRAS mutations are associated with proliferative thyroid lesions., NRAS mutations in myeloma patients were associated with a significantly lower response rate to single-agent bortezomib., MAF has a role in mediating crosstalk between Ras-MAPK and mTOR signaling in NF1, NRAS isoforms differentially affect downstream pathways, cell growth, and cell transformation., prognosis of patients with melanoma expressing constitutively active N-RAS is poor, Somatic N-RAS G38A-->Gly13Asp substitution was restricted to hematopoietic cells, NRAS mutations and KIT amplifications occur in melanomas originating from the vulva or vagina, Missense mutation in NRAS is associated with concurrent juvenile myelomonocytic leukemia and T-lymphoblastic lymphoma., Mutations in NRAS predict resistance to anti-EGFR therapies., the outcome of 68 patients with advanced colorectal cancer and RAS, BRAF and PI3KCA status according to ALK gene status, is reported., Mutations of N-ras are present in multiple congenital neavi. A nonsense mutation afects the codon 61 N-ras., mutations in BRAF and NRAS are not mutually exclusive because they were simultaneously present in the same tumor specimens, NRAS mutation is associated with melanoma., In cytogenetically normal acute myeloid leukemia, activating N-RAS mutations in codons 12, 13, or 61 were detected in 22 of 204 patients., This review will point attention on Neuroblastoma-RAS (NRAS) status in metastatic CRC (mCRC) patients (pts) selected for anti-EGFR therapy, This study indicated that mutations of KRAS, PIK3CA and NRAS were rare in advanced gastric cancer., analysis of RAS, RET/PTC, and BRAF mutations in advanced stage of papillary thyroid carcinoma, NRAS mutations were more prevalent than KIT mutations in a series of melanomas arising from the female urogenital tract., NRAS mutations affect metastatic colorectal cancer patients' prognosis and predict lack of response to EGF receptor antagonists., Characteristics and prognosis of colorectal cancer with NRAS mutations are different from those with KRAS or BRAF mutations., RAS mutation, especially a NRAS codon 61 mutation, was significantly associated with the distant metastasis in follicular thyroid carcinoma, The high-resolution melting method developed was shown to be a reliable method for NRAS mutation detection, NRAS mutation is associated with melanoma nodal metastases and an unknown primary site., BET inhibition with I-BET151 appears independent of the BRAF and NRAS mutational status of melanoma, BRAF and NRAS mutation status does not influence survival in metastatic melanoma., our data suggest that the genetic background in melanoma cells influences the response to inhibitors blocking de novo DNA synthesis, and that defining the RAS mutation status could be used to stratify patients for the use of antifolate drugs., amuvatinib has proapoptotic activity against melanoma cell lines, with selectivity observed for those harboring oncogenic NRAS but not BRAF, TBK1 promotes the malignant properties of NRAS-mutant melanoma and its targeting., Clinicopathologic characteristics, survival outcomes, functional impact, and gene expression profiling were similar between patients with KRAS 12/13 and those with NRAS or KRAS 61/146-mutated colorectal cancers, No association was found between NRASQ61R mutation and melanoma risk factors or melanoma-specific survival., NRAS expression and increased MAPK activation drive vemurafenib resistance in V600E BRAF+ve melanoma., NRAS and KRAS mutations have a role in Down syndrome acute lymphoblastic leukemia that lacks JAK2 mutations, RAS mutations in indeterminate thyroid nodules have a role in follicular variant of papillary thyroid carcinoma, These results provide a rationale for targeting mutant RAS or PI3K/AKT/mTOR signaling in the subset of Eedheim Chester disease patients with NRAS or PIK3CA mutations., Ras-tyrosine 32 serves as an Src-dependent keystone regulatory residue that modulates Ras GTPase activity and ensures unidirectionality to the Ras GTPase cycle., acylation state of Ras proteins (H-Ras and N-Ras) controls not only their distribution between the Golgi apparatus and the plasma membrane, but also their distribution within the Golgi stacks., Targeted sequencing on primary, metastatic, and normal tissue from colorectal cancer patients found a high degree of concordance for KRAS, NRAS, and BRAF mutations that were identical in both the primary and metastatic tumors., NRAS mutations are associated with acute leukemia., NRAS mutation is associated with response to chemotherapy in colorectal liver metastases., This work explains the curious predominance in human melanoma of mutations of codon 61 of NRAS over other oncogenic NRAS mutations. we show that physiologic expression of NRASQ61R, but not NRASG12D, drives melanoma formation., report the cases of two children, presenting a melanocytic lesion located on the ear with an exon 3 NRAS mutation, Analysis of the gene-expression patterns of leukemic subpopulations revealed that the NRAS(G12V)-mediated leukemia self-renewal signature is preferentially expressed in the leukemia stem cell-enriched subpopulation., Our findings suggest that NRAS is an oncogenic driver in serous ovarian tumors., Report NRAS mutation status in colorectal neoplasms and neuroendocrine differentiation in primary/metastatic colorectal neoplasms., NRAS expression is required for the proliferative advantage of human AML cell lines in vitro and for the maintenance of mouse Nras-mutant AML in vivo, BRAF and NRAS alterations are preserved during in vitro culture in melanoma in a series of patients in which the c-KIT mutation was not detected, This expert group recommends testing for KRAS and NRAS status in all patients with metastatic CRC being considered for anti-epidermal growth factor receptor (anti-EGFR) therapy, Results show that mutated NRAS is associated with melanomas that are more aggressive., Study sequenced a large clinical series of patients with metastatic colorectal cancer (mCRC) for RAS and PIK3CA mutations. RAS alterations occurred in 48% of mCRC cases, with mutations within KRAS exon 2 in 43%, KRAS exons 3 and 4 in 3%, and NRAS in 2% of cases. PIK3CA mutations occurred in about 10% of mCRC and were significantly associated with concurrent RAS mutation., suggests that PIK3CA mutations account for a small fraction of PI3K pathway activation and have a limited impact in interfering with the BRAF/NRAS-driven growth in melanoma, The combination of PRi + MEKi can be an effective regimen for blocking proliferation of NRAS mutant melanomas., We aimed to assess the diagnostic accuracy of an immunohistochemistry using a noel anti-NRAS monoclonal antibody on the samples from patients with metastatic melanoma., NRAS mutations are associated with Metastatic Colorectal Cancer., RAS mutations cause vascular tumors including pyogenic granuloma, The CM cell lines, as well as the tumor xenografts and their metastases, were positive for the melanoma markers HMB-45, S100B, and MART-1. Two cell lines and their corresponding xenografts carried a BRAF mutation, the third showed an NRAS mutation., NRAS mutations in advanced melanoma correlate with increased benefit from immune-based therapies compared with other genetic subtypes., NRAS mutation is not associated response to chemotherapy in melanoma., Combination strategies of immune and targeted therapies may also play a role in the future although clinical trials testing these approaches are in early stages., Activated NRAS and aberrant Wnt signaling conspire to drive congenital melanocytic nevus syndrome., NRAS mutations are usually present in the majority of metastatic colorectal cancer cells., studied 269 Chinese (mostly Han) with de novo AML. FLT3-ITD was detected in 51 subjects (23%; 95% CI, 17-28%), R882 mutation of DNMT3A in 17 (6%; 95% CI, 3-9%) and NRAS mutation in 17 (7%; 95% CI, 3-9%)., Among 264 patients, mutations in KRAS exon 2, KRAS exons 3 or 4, NRAS, BRAF and PIK3CA were detected in 34.1%, 3.8%, 4.2%, 5.4% and 6.4%, respectively. Thus, a total of 12.1% of patients without KRAS exon 2 mutations had other RAS mutations, somatic mosaicism for a mutation accounts for disparate phenotypes in RAS-associated leukoproliferative disease, AML with inv(16) and NRAS mutation have a differentiation gene signature, In the title., NRAS gene mutation was significantly associated with lung metastasis., Case Report, NRAS activating mutation is relatively low in Korean colorectal cancer patients., RAS mutation targeting the Korean population showed 45.7% frequency in follicular-derived thyroid neoplasms., ABL phosphorylates tyrosine 137 of H-, K-, and NRAS., Meta-analysis, BRAF, NRAS and KRAS gene mutations in plasma cell dyscrasias may have a role MEK-ERK pathway activation, Mutations in NRAS have been identified in approximately 15-20% of melanomas., Report 3-fold increased risk of death for higher-risk melanomas harboring NRAS or BRAF mutations., NRASQ61K mutation is associated with recurrence in Neuroblastoma., Evaluation of mutations in NRAS exons 2, 3, and 4-can define the patient with metastatic Colorectal cancer that is unlikely to benefit from anti- Epidermal Growth Factor Receptor therapy., The prevalence of oncogenic RAS mutations was higher among Arab Asian children than in other countries. RAS mutations in AML were found to coexist with other genetic aberrations, particularly MLL rearrangement, BRAF mutations are infrequent, whereas C-KIT and NRAS mutations are seen with higher frequency in vulvar melanomas than melanomas of other sites., RAS-positive thyroid nodules, especially in older individuals, frequently demonstrate a benign phenotype.Cytologically benign nodules, even if RAS-positive, may be candidates for a non-operative observational strategy, comparison of the GTPase reaction of the slower hydrolyzing GTPase Ran with Ras, mutations found in face and palm or sole melanoma in Japanese patients, NRASQ61R and BRAFV600E immunohistochemistry coupled with next-generation sequencing allow detection of mutations in melanoma challenging samples., NRAS mutation was associated with a worse disease evolution in a selected cohort of patients affected by pulmonary metastases of malignant melanoma., Studies indicate that KRAS and NRAS mutations are currently recognized as the best predictive factors for primary resistance to anti-EGFR monoclonal antibodies., Data suggest that Src kinases inhibitors may act with different mechanisms in non-small cell lung cancer (NSCLC) depending on EGF receptor (EGFR)/Ras protein (Ras) mutational profile., let-7 is a tumor suppressor that negatively regulates RAS, also in Ewing Sarcoma, and HIF-1alpha may contribute to the aggressive metastatic behavior of Ewing Sarcoma, NRAS Mutation is associated with response to therapy in Advanced Melanoma., Case report and review analyses showed that NRAS c.179G > A mutation is associated with familial Noonan Syndrome and predispose to hyperpigmented lesions., The neutron crystal structure presented here puts in question our understanding of the pre-catalytic state associated with the hydrolysis reaction central to the function of RAS and other GTPases., study concluded that 26% of patients had detectable FLT3-ITD or RAS mutation at transformation from myelodysplastic syndrome to acute myeloid leukemia, and these mutations were associated with very poor outcome, analysis of HRAS, KRAS and NRAS expression in colorectal tumor cells, Data indicate that mutations in PTEN phosphatase A167T and NRAS protein Q61L, and proto-oncogene protein BRAF V600E were detected in melanoma cell line., Data show that tet methylcytosine dioxygenase 2 TET2, isocitrate dehydrogenases 1/2 IDH1/IDH2, serine/arginine-rich splicing factor 2 SRSF2, splicing factor 3b subunit 1 SF3B1, and ras proteins (KRAS/NRAS) are not conserved in dog mast Cell tumors., Data show that 11/105 patients failed all molecular analysis, The patient's resected brain tumor is BRAF V600E mutated, NRAS wild type (WT), and TERT C250T mutated. The patient is a carrier of germline variants in immunomodulatory loci associated with prolonged survival., ABHD17 catalytic activity is required for N-Ras depalmitoylation and re-localization to internal cellular membranes., MC1R status is associated with BRAF(V600E), BRAF(V600K), and NRAS mutations in cutaneous melanomas,
OFFICIAL_GENE_SYMBOL NRAS,
OMIM_DISEASE Colorectal cancer, somatic, Melanocytic nevus syndrome, congenital, somatic, Epidermal nevus, somatic, Schimmelpenning-Feuerstein-Mims syndrome, somatic mosaic, Thyroid carcinoma, follicular, somatic, Neurocutaneous melanosis, somatic, Noonan syndrome 6, RAS-associated autoimmune lymphoproliferative syndrome type IV, somatic,
SP_COMMENT disease:Defects in NRAS are a cause of juvenile myelomonocytic leukemia (JMML) [MIM:607785]. JMML is a pediatric myelodysplastic syndrome that constitutes approximately 30% of childhood cases of myelodysplastic syndrome (MDS) and 2% of leukemia., disease:Mutations which change AA 12, 13 or 61 activate the potential of Ras to transform cultured cells and are implicated in a variety of human tumors., enzyme regulation:Alternate between an inactive form bound to GDP and an active form bound to GTP. Activated by a guanine nucleotide-exchange factor (GEF) and inactivated by a GTPase-activating protein (GAP)., function:Ras proteins bind GDP/GTP and possess intrinsic GTPase activity., online information:NRAS mutation db, online information:RAS proteins entry, PTM:Palmitoylated by the ZDHHC9-GOLGA7 complex. A continuous cycle of de- and re-palmitoylation regulates rapid exchange between plasma membrane and Golgi., similarity:Belongs to the small GTPase superfamily. Ras family., subcellular location:Shuttles between the plasma membrane and the Golgi apparatus.,
related RAS viral (r-ras) oncogene homolog 2(RRAS2) related RAS viral (r-ras) oncogene homolog 2(RRAS2) Related Genes Homo sapiens
CHROMOSOME 1, 11,
CYTOBAND 11p15.2, 1p32.3,
ENSEMBL_GENE_ID ENSG00000133818,
GENERIF_SUMMARY TGF-beta and TC21 have roles in tumorigenesis, TC21 directly links antigen receptors to PI(3)K-mediated survival pathways., RasGRF GEFs can activate TC21 in all sublocalizations except the Golgi complex. Farnesylated TC21 can be activated by RasGRF1 & RasGRF2, but geranylgeranylated TC21 is unresponsive to RasGRF2., Suggest that TC21 promotes cell motility and metastasis by regulating the expression of E-cadherin and N-cadherin in hepatocellular carcinoma and is associated with tumor progression and poor prognosis in HCC., This article is the first study demonstrating expression of TC21 in human skin malignant tumors and suggests that TC21 is more expressed in highly aggressive skin tumors., R-RAS2 is overexpressed in the early stages of malignancy in tumors of the human central nervous system., R-Ras2 has a role in both primary breast tumorigenesis and the late metastatic steps of cancer cells in the lung parenchyma.,
OMIM_DISEASE Ovarian carcinoma,
SP_COMMENT disease:Defects in RRAS2 are associated with ovarian cancer [MIM:167000]. Ovarian cancer is the leading cause of death from gynecologic malignancy. It is characterized by advanced presentation with loco-regional dissemination in the peritoneal cavity and the rare incidence of visceral metastases. These typical features relate to the biology of the disease, which is a principal determinant of outcome., function:It is a plasma membrane-associated GTP-binding protein with GTPase activity. Might transduce growth inhibitory signals across the cell membrane, exerting its effect through an effector shared with the Ras proteins but in an antagonistic fashion., PTM:May be post-translationally modified by both palmitoylation and polyisoprenylation., similarity:Belongs to the small GTPase superfamily. Ras family., subcellular location:Inner surface of plasma membrane possibly with attachment requiring acylation of the C-terminal cysteine (By similarity with RAS)., tissue specificity:Ubiquitously present in all tissues examined, with the highest levels in heart, placenta, and skeletal muscle. Moderate levels in lung and liver; low levels in brain, kidney, and pancreas.,
related RAS viral (r-ras) oncogene homolog(RRAS) related RAS viral (r-ras) oncogene homolog(RRAS) Related Genes Homo sapiens
CHROMOSOME 19,
CYTOBAND 19q13.3-qter,
ENSEMBL_GENE_ID ENSG00000126458,
GENERIF_SUMMARY study of the potential contribution in generating of estrogen-independence in MCF-7 cells, R-Ras promotes focal adhesion formation by signaling to FAK and p130(Cas) through a novel mechanism that differs from but synergizes with the alpha2beta1 integrin., the oncogene R-Ras promotes tumor growth of cervical epithelial cells and increases their migration potential over collagen through a pathway that involves PI 3-K., activation of R-Ras promotes the formation of focal adhesions and a spread cell shape, Plexin-B1 mediates Sema4D-induced repulsive axon guidance signaling by acting as a GTPase activating protein for R-Ras, R-Ras plays a key role in cell migration by locally regulating the switch from Rac to Rho activity after membrane protrusion and adhesion, GPCRs rapidly activate R-Ras; R-Ras activation by the GPCRs is apparently directly induced by cyclic AMP-regulated Epac proteins; and activated R-Ras specifically controls GPCR-mediated phospholipase D stimulation, These findings show that R-Ras activity mediates inhibition of insulin signaling associated with suppression of estrogen action, implicating this GTPase in a growth-inhibitory mechanism associated with antiestrogen treatment of breast cancer., R-Ras and ILK have roles upstream of GSK-3beta in the regulation of neuronal polarity, Notch1 ligand, Delta-like ligand-4, stimulates R-Ras-dependent alpha 5 beta 1 integrin-mediated adhesion, demonstrating the physiological relevance of this pathway., results map the functional elements in the R-ras promoter sequence and suggest that the GABP may be critical for transcription of R-ras and for maintenance of normal blood vessel functions through the regulation of this gene, TCF8 activates R-Ras, another class of angiogenic regulator, to suppress angiogenesis by a mechanism other than a transcriptional attenuator., the monomeric intracellular plexin-B1 binds R-Ras but not H-Ras. These findings suggest that the monomeric form of the intracellular region is primed for GAP activity and extend a model for plexin activation., Sema3E acts on plexin D1 to initiate a two-pronged mechanism involving R-Ras inactivation and Arf6 stimulation, which affect the status of activation of integrins and their intracellular trafficking, respectively., data support a model in which R-Ras functionally associates with FLNa and thereby regulates integrin-dependent migration, Data suggest that the RRAS gene is an important regulatory module in the pathogenesis of biliary atresia (BA), which may serve as a novel prognostic marker for BA., Maintaining endothelial barrier function is dependent upon active R-Ras and association between R-Ras and FLNa., These findings identify R-Ras as a critical regulator of vessel integrity and function during tumor vascularization., These data suggest that pharmacological inhibition of RRAS signaling may confer therapeutic benefit in Huntington's disease., A polymorphism linked to RRAS, SCAF1, IRF3 and BCL2L12 genes is associated with cirrhosis in hepatitis C virus carriers., Contradicting the positive association reported in previous studies, our results indicate that R-Ras activation may negatively regulate the transformation of breast epithelial cells., Evidence is provided of a functional link between RRAS and MAPK signalling and reveal an unpredicted role of enhanced RRAS function in human disease., Patients with gemistocytic astrocytomas with an RRAS deletion tend to have shorter survival rates than those without deletion., phosphorylation of ORP3 controls its association with VAPA. Furthermore, ORP3-VAPA complexes stimulate R-Ras signaling., Girdin regulates the trafficking of VE-cadherin in synergy with R-Ras., RRAS is a key regulator of miR-34/449 promotion of actin network formation during multiciliogenesis., Suggest that R-Ras regulates angiogenic activities of endothelial cells in part via inhibition of the p38MAPK-HSP27 axis of VEGF signaling.,
SP_COMMENT function:Regulates the organization of the actin cytoskeleton., similarity:Belongs to the small GTPase superfamily. Ras family., subcellular location:Inner surface of plasma membrane possibly with attachment requiring acylation of the C-terminal cysteine (By similarity with RAS)., subunit:Interacts with PLCE1.,