Database for Annotation, Visualization and Integrated Discovery 2.1
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A-Raf proto-oncogene, serine/threonine kinase(ARAF) A-Raf proto-oncogene, serine/threonine kinase(ARAF) Related Genes Homo sapiens
CHROMOSOME X,
CYTOBAND Xp11.4-p11.2,
ENSEMBL_GENE_ID ENSG00000078061,
GENERIF_SUMMARY In a two-hybrid screen of human fetal liver cDNA library, TH1 was detected as a new interaction partner of A-Raf; this specific interaction may have played a critical role in the activation of A-Raf., A-Raf kinase is negatively regulated by trihydrophobin 1, mutation analysis of the conserved regions in the ARAF gene in human colorectal adenocarcinoma, A-Raf residues are identified that bind to specific phosphoinositides, possibly as a mechanism to localize the enzyme to particular membrane microdomains rich in these phospholipids., These data reveal that B-RAF is an important mediator of neuronal survival, migration, and dendrite formation and that A-RAF cannot fully compensate for these functions., Positive regulation of A-RAF by phosphorylation of isoform-specific hinge segment and identification of novel phosphorylation sites., hnRNP H blocks MST2-mediated apoptosis in cancer cells by regulating A-Raf transcription., study investigated role of ARAF in cancer cell signaling and examined the role of ARAF in mediating paradoxical activation of the MAPK pathway in cells treated with RAF inhibitors; ARAF seems to stabilize BRAF, Ras pathway activation via EGF treatment induced strong binding between B-Raf and C-Raf and a low level of binding between B-Raf and A-Raf., show that Araf antagonizes mesendoderm induction and patterning activity of Nodal/Smad2 signals in vertebrate embryos by directly inhibiting Smad2 signalling, Galpha12-ARAF-ERK pathway stimulates RFFL transcription through the transcription factor c-Myc., The study identifies somatic activating ARAF mutations in Langerhans cell histiocytosis., Dimerization of the kinase ARAF promotes MAPK pathway activation and cell migration., analysis of FGFR2-PPHLN1 fusion and ARAF mutations in intrahepatic cholangiocarcinoma, Aberrant expression of A-, B-, and C-RAF, and COT is frequent in PTC; increased expression of COT is correlated with recurrence of PTC., This review discusses the regulation of A-Raf protein expression, and the roles of A-Raf in apoptosis and cancer, with a special focus on its role in resistance to Raf inhibitors. [review], A-Raf interacts with MEK1 and activates MEK1 by phosphorylation.,
OFFICIAL_GENE_SYMBOL ARAF,
SP_COMMENT catalytic activity:ATP + a protein = ADP + a phosphoprotein., cofactor:Binds 2 zinc ions per subunit., function:Involved in the transduction of mitogenic signals from the cell membrane to the nucleus., similarity:Belongs to the protein kinase superfamily., similarity:Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. RAF subfamily., similarity:Contains 1 phorbol-ester/DAG-type zinc finger., similarity:Contains 1 protein kinase domain., similarity:Contains 1 RBD (Ras-binding) domain., subunit:Interacts with TH1L/NELFD., tissue specificity:Predominantly in urogenital tissues.,
B-Raf proto-oncogene, serine/threonine kinase(BRAF) B-Raf proto-oncogene, serine/threonine kinase(BRAF) Related Genes Homo sapiens
CHROMOSOME 7,
CYTOBAND 7q34,
ENSEMBL_GENE_ID ENSG00000157764,
GENERIF_SUMMARY somatic missense mutations in 66% of malignant melanomas and at lower frequency in a wide range of human cancers, BRAF mutations in colorectal cancers occur only in tumours that do not carry mutations in a RAS gene known as KRAS, and BRAF mutation is linked to the proficiency of these tumours in repairing mismatched bases in DNA, High frequency of BRAF mutations in nevi, The V599E BRAF mutation appears to be a somatic mutation associated with melanoma development and/or progression in a proportion of affected individuals., 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, High prevalence of BRAF mutations in thyroid cancer is genetic evidence for constitutive activation of the RET/PTC-RAS-BRAF signaling pathway in papillary thyroid carcinoma., activating BRAF mutations may be an important event in the development of papillary thyroid cancer, cAMP activates ERK and increases proliferation of autosomal dominant polycystic kindey epithelial cells through the sequential phosphorylation of PKA, B-Raf and MAPK in a pathway separate from the classical receptor tyrosine kinase cascade, gene is mutated in skin melanoma, but not in uveal melanomas, 13 germline BRAF variants, 4 of which were silent mutations in coding regions & 9 nucleotide substitutions in introns, were found in melanoma patients and melanoma family, but none appeared statistically likely to be a melanoma susceptibility gene., B-raf is involved in adhesion-independent ERK1/2 signaling in melanocytes, Data suggest that BRAF T1796A activating mutation is not common in primary uveal melanoma., B-Raf has a role in extracellular signal-regulated kinase (ERK) signaling in T cells and prevents antigen-presenting cell-induced anergy, BRAF has a role in in squamous cell carcinoma of the head and neck through uncommon mutations, The BRAF(V599E) mutation appears to be an alternative event to RET/PTC rearrangement rather than to RAS mutations, which are rare in PTC. BRAF(V599E) may represent an alternative pathway to oncogenic MAPK activation in PTCs without RET/PTC activation., Mucinous ovarian cancers without a KRAS mutation have not sustained alternative activation of this signaling pathway through mutation of the BRAF oncogene., 3 cell lines derived from human choroidal melanoma express B-Raf containing the V599E mutation and showed a 10-fold increase in endogenous B-RafV599E kinase activity and a constitutive activation of the MEK/ERK pathway that is independent of Ras, Mutations are not detectable in plasma cell leukemia and multiple myeloma., mutation of BRAF gene could be a potentially useful marker of prognosis of patients with advanced thyroid cancers, Our findings of a high frequency of BRAF mutations at codon 599 in benign melanocytic lesions of the skin indicate that this mutation is not sufficient by itself for malignant transformation., Both BRAF and FBXW7 mutations functionally activate kinase effectors important in pancreatic cancer and extend potential options for therapeutic targeting of kinases in treatment of phenotypically distinct pancreatic adenocarcinoma subsets., BRAF mutations, which are present in a variety of other human cancers, do not seem to be involved in gastric cancer development, Uceal melanomas arise independent of oncogenic BRAF and NRAS mutations., BRAF mutations were seen in stomach neoplasms., BRAF mutations are restricted to papillary carcinomas and poorly differentiated and anaplastic carcinomas arising from papillary carcinomas, BRAF is occasionally mutated in NHL, and BRAF mutation may contribute to tumor development in some NHLs, None of the cases of gastric cancer showed braf mutations, Mutations of BRAF are associated with extensive hMLH1 promoter methylation in sporadic colorectal carcinomas, Missense mutation is marker of colonic but not gastric cancer., Mutations were found in exon 15 in colorectal adenocarcinoma., Our data indicate that BRAF gene mutations are rare to absent events in uveal melanoma of humans., NRAS and BRAF mutations arise early during melanoma pathogenesis and are preserved throughout tumor progression, BRAF mutations are associated with proximal colon tumors with mismatch repair deficiency and MLH1 hypermethylation., New enriched PCR-RFLP assay for detecting mutations of BRAF codon 599 mutation in pleural mesotheliomas., 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, BRAF mutations are frequently present in sporadic colorectal cancer with methylated hMLH1, Mutations in BRAF 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., The lack or low prevalence of BRAF mutation in other thyroid neoplasms is consistent with the notion that other previously defined genetic alterations on the same signaling pathway are sufficient to cause tumorigenesis in most thyroid neoplasms., possible cooperation between BRAF activation and PTEN loss in melanoma development., mutations in the BRAF gene and to some extent in the N-ras gene represent early somatic events that occur in melanocytic nevi, BRAF mutation may be acquired during development of metastasis but is not a significant factor for primary melanoma development and disease outcome., ovarian serous cystadenomas do not contain mutations in either BRAF or KRAS genes, These results suggest that the BRAF mutation is unlikely to be involved in gastric carcinogenesis., BRAF(V599E) is more common genetic alteration found to date in adult sporadic papillary thyroid carcinomas (PTCs). It is unique for this thyroid cancer histotype, and it might drive the development of PTCs of classic papillary subtype., The finding of tandem mutations in thin melanomas makes it more likely that they arise as a simultaneous rather than sequential event., Radiation-induced tumors have a low prevalence of BRAF point mutations and high prevalence of RET/PTC rearrangements, B-Raf kinase activity regulation by tuberin and Rheb is mammalian target of rapamycin (mTOR)-independent, mucosal melanomas of the head and neck do not frequently harbor an activating mutation of BRAF, in contrast to cutaneous melanoma, BRAF does not appear to be involved in the pathogenesis of uveal melanoma, BRAF mutations are rather rare in solitary cold adenomas and adenomatous nodules and do not explain the molecular etiology of ras mutation-negative cold thyroid nodules., activation of this gene may be one of the early events in the pathogenesis of some melanomas., B-Raf and ERK are activated by cyclic AMP after calcium restriction, mutated in papillary thyroid cancer., In this study, this BRAF mutation was demonstrated in some conjunctival melanoma tissue samples, suggesting that some conjunctival melanomas may share biological features in common with cutaneous melanoma., Data suggest that SPRY2, an inhibitor of ERK signaling, may be bypassed in melanoma cells either by down-regulation of its expression in WT BRAF cells, or by the presence of the BRAF mutation., Mutations within the BRAF gene are useful markers for the differential diagnosis between Spitz nevus and malignant melanoma., we found 19 cases (38%) to harbor somatic B-raf exon 15 mutations., Data provide evidence that B-Raf is a positive regulator of T cell receptor-mediated sustained ERK activation, which is required for NFAT activation and the full production of IL-2., BRAF(V599E) mutation is seven times higher in lesions with structural changes and 13 times higher in growing lesions as compared with lesions without changes, REVIEW, 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., mutated in childhood acute lymphoblastic leukemia., BRAF mutations are associated with conjunctival neoplasms, AKAP9-BRAF fusion was preferentially found in radiation-induced papillary carcinomas developing after a short latency, whereas BRAF point mutations were absent in this group, Data suggest that Rit is involved in a novel pathway of neuronal development and regeneration by coupling specific trophic factor signals to sustained activation of the B-Raf/ERK and p38 MAP kinase cascades., a novel Ras-independent ERK1/2 activation system in which p110gamma/Raf-1/MEK1/2 and PKA/B-Raf/MEK1/2 cooperate to activate ERK1/2., 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., KSHV-infected cell lines expressed higher levels of B-Raf and VEGF-A; B-Raf-induced VEGF-A expression was demonstrated to be sufficient to enhance tubule formation in endothelial cells, autoinhibition was negatively regulated by acidic substitutions at phosphorylation sites within the activation loop, Mutations in the BRAF protooncogene (V599E)may be an alternative pathway of tumorigenesis of familial colorectal cancer., BRAF mutations proved to be absent in tumors from hereditary nonpolyposis colorectal cancer syndrome (HNPCC) families with germline mutations in the MMR genes MLH1 and MSH2., The data of this study suggest that activating mutations of B-RAF are not a frequent event in gliomas; nevertheless, when present they are associated with high-grade malignant lesions., B-raf mutations surrounding Thr439 found in human cancers are unlikely to contribute to increased oncogenic properties of B-raf, These results suggest that BRAF mutations do not have a role in tumorigenesis of neuroendocrine gastroenteropancreatic tumors., Anaplastic thyroid carcinomas which are derived from papillary carcinomas are due to BRAF and p53 mutations, B-raf V599E and V599K oncogenic mutations are likely to affect melanocyte-specific pathways controlling proliferation and differentiation, The increasing frequency of BRAF mutations as a function of age could help account for the well documented but poorly understood observation that age is a relevant prognostic indicator for patients with papillary thyroid carcinoma., BRAF mutation occurs later in thyroid tumor progression and is restricted mainly to papillary thyroid carcinoma and anaplastic thyroid carcinoma, Role of BRAF mutation in facilitating metastasis and progression of papillary thyroid cancer in lymph nodes., determination of mutation specific gene expression profiles in papillary thyroid carcinoma, Single-cell clones with efficient knockdown of (V 600 E)B-RAF could be propagated in the presence of basic fibroblast growth factor but underwent apoptosis or senescence-like growth arrest upon withdrawal of this growth factor, sustained BRAF(V600E) expression in human melanocytes induces cell cycle arrest, which is accompanied by the induction of both p16(INK4a) and senescence-associated acidic beta-galactosidase (SA-beta-Gal) activity, a commonly used senescence marker, BRAF mutation in melanoma is most likely to occur prior to the development of metastatic disease, 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, The results showed that conjunctival nevi, similar to skin nevi, have a high frequency of oncogenic BRAF mutations., These data suggest that MITF is an anti-proliferation factor that is down-regulated by B-RAF signaling and that this is a crucial event for the progression of melanomas that harbor oncogenic B-RAF., Mutations of the BRAF gene are partly involved in the malignant transformation of the endometrium., selective reduction in catalytic activity and expression of B-Raf but not Raf-1 suggest that B-Raf may be playing an important role in altered ERK signaling in brain of suicide subjects, and thus in the pathophysiology of suicide, In patients with papillary thyroid cancer, BRAF mutation is associated with poorer clinicopathological outcomes and independently predicts recurrence., As the BRAF oncogene is frequently found to be mutated in human cutaneous melanomas, it may constitute a risk factor for melanoma formation within CMN and DMN., The oncogenic B-raf mutations V599E and V599K, as early events in melanocyte transformation, persist throughout metastasis with important prognostic implications., copy number gain may represent another mechanism of BRAF activation in thyroid tumors, The estimated proportion of attributable risk of melanoma due to variants in BRAF is 1.6%, but the burden of disease associated with this variant is greater than that associated with the major melanoma locus (CDKN2A) which has a risk of 0.2%., Mutation and elevated expression of BRAF is associated with the development of testicular germ cell tumors, The authors have developed and run a high-throughput screen to find inhibitors of V600E BRAF using an enzyme cascade assay in which oncogenic BRAF activates MEK1, which in turn activates ERK2, which then phosphorylates the transcription factor ELK1., Data suggest that B-RAF activates C-RAF through a mechanism involving 14-3-3 mediated heterooligomerization and C-RAF transphosphorylation., V600E B-Raf requires the Hsp90 chaperone for stability and is degraded in response to Hsp90 inhibitors., activating mutations of PDGFR-alpha, c-kit and B-RAF are absent in gliosarcomas, V599E BRAF mutation was uncommon in Japanese lung cancer., aberrant B-Raf activity in angiomyolipomas leads to abnormal cellular differentiation and migration [review], The most frequent B-RAF gene alterations are not involved in prostate carcinogenesis, BRAF mutation does not seem to be sufficient to produce MAPK activation in melanocytic nevi., gain-of-function BRAF signaling is strongly associated with in vivo tumorigenicity, findings demonstrate that heterogeneous de novo missense mutations in three genes within the mitogen-activated protein kinase pathway, BRAF, MEK1 and MEK2 cause cardio-facio-cutaneous syndrome, wild-type B-Raf-mediated ERK1/2 activation plays a major role in proliferation and transformation of uveal melanocytes; Raf-1 is not involved in this activation, NRAS and BRAF activating mutations can coexist in the same melanoma, but are mutually exclusive at the single-cell level, Cardio-facio-cutaneous (CFC) syndrome involves dysregulation of the RAS-RAF-ERK pathway., Merlin and MLK3 can interact in situ and merlin can disrupt the interactions between B-Raf and Raf-1 or those between MLK3 and either B-Raf or Raf-1., Melanoma cells require either B-RAF or phosphoinositide-3 kinase activation for protection from anoikis., BRAF V600E is associated with a high risk of recurrence and less differentiated papillary thyroid carcinoma due to the impairment of Na+/I- targeting to the membrane, UV light is not necessarily required for the acquisition of the BRAF(V600E) mutation, and non-mutagenic effects of UV light to melanocytes may be more important in the nevogenesis, BRAF mutations are as uncommon as KRAS mutations in prostate adenocarcinoma, B-RAF (V600E) was confirmed to be associated with the papillary growth pattern, but not with poorer differentiated papillary thyroid carcinoma variants., among 23 melanomas located at body sites with chronic UV exposure, only a single tumour harboured the B-raf V599E mutation which was a significantly lower frequency in comparison to melanomas from sun-protected body sites, a BRAFT1799A mutation may have a role in poor differentiation of thyroid carcinoma, A subset of Spitz nevi, some with atypical histologic features, possess BRAF mutations. The BRAF mutational status does not separate all Spitz nevi from spitzoid melanomas and non-Spitz types of melanocytic proliferations, contrary to previous reports., Rheb has a central role in the regulation of the Ras/B-Raf/C-Raf/MEK signaling network, CpG island methylator phenotype-positive colorectal tumors represent a distinct subset, encompassing almost all cases of tumors with BRAF mutation, findings show that MC1R variants are strongly associated with BRAF mutations in non-chronic sun-induced damage melanomas; in this subtype, risk for melanoma associated with MC1R is due to increase in risk of developing melanomas with BRAF mutations, BRAF mutation is associated with melanoma and melanocytic nevi., Thus, we propose that the hitherto unidentified function of the B-Raf amino-terminal region is to mediate calcium-dependent activation of B-Raf and the following MEK activation, which may occur in the absence of Ras activation., Aberrant methylation and hence silencing of TIMP3, SLC5A8, DAPK and RARbeta2, in association with BRAF mutation, may be an important step in PTC tumorigenesis and progression., BRAF mutation was frequent in hyperplastic polyps (67%) and sessile serrated adenomas (81%)., B-RAF has been identified as the most mutated gene in invasive cells and therefore an attractive therapeutic target in melanoma., BRAF mutations are associated with colorectal cancers, Expression of p27Kip1 in melanoma is regulated by B-RAF at the mRNA level and via B-RAF control of Cks1/Skp2-mediated proteolysis., Single nucleotide polymorphism found exclusively in papillary thyroid carcinoma., BRAF, K-ras and BAT26 are expressed in colorectal polyps and stool, BRAF, K-ras and BAT26 are expressed in colorectal polyps and stool [BAT26], Braf mutations in thyroid tumorigenesis., 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, BRAFV600E activates not only MAPK but also NF-kappaB signaling pathway in human thyroid cancer cells, leading to an acquisition of apoptotic resistance and promotion of invasion., Expression of active mutants of B-Raf induces fibronectin., Extracellular signal-regulated kinase-3 (ERK3/MAPK6) is highly expressed in response to BRAF signaling., BRAF T1976A mutation is present at high frequency in benign naevi such as Spitz and Reed., data support a model in which mutational activation of BRAF in human melanomas contributes to constitutive induction of NF-kappaB activity and to increased survival of melanoma cells, Normally, BRAF alone is responsible for signaling to MEK. However, when RAS is mutated in melanoma, melanocytes switch their signaling from BRAF to CRAF., Activating BRAF mutation is associated with papillary thyroid carcinoma, BRAF mutation remained a significant prognostic factor for lymph node metastasis (odds ratio = 10.8, 95% confidence interval, 3.5-34.0, P < 0.0001)., phosphorylation on both S365 and S429 participate in the differential regulation of B-Raf isoforms through distinct mechanisms, data provide evidence that oncogenic properties of BRAF contribute to the tumorigenesis of intraductal papillary mucinous neoplasm/carcinoma (IPMN/IPMC), but at a lower frequency than KRAS, BRAF-V600E mutations are mainly involved in colorectal cancer families characterized by an increased risk of other common malignancies, Association with preexisting nevi and pronounced infiltration of lymphocytes was significantly higher in BRAF mutated melanoma tumours, Previously identified associations between smoking and colon cancer, whether microsatellite unstable or stable, appear to be explained by the association of smoking with BRAF mutation., BRAF(T1799A) mutation is associated with a lower rate of tumor proliferation., 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, The role for BRAF activation in thyroid cancer development and establishing the potential therapeutic efficacy of BRAF-targeted agents in patients with thyroid cancerwill be reviewed., BRAF mutation is associated with thyroid carcinogenesis, there is a subgroup of colorectal carcinomas which develop via the microsatellite instability pathway that carry an alteration of the BRAF gene, Absence of association between BRAF mutation and activation of MAPK pathway in papillary thyroid carcinoma suggests the presence of mechanisms that downregulate MAPK activation., Copy gain of PDGFB occurs in a subset of tumors showing no evidence of mutated BRAF or rearranged ret, suggesting that copy gain of PDGFB may underlie the increased expression of platelet-derived growth factor described recently in the literature., characterization of the T1799-1801del and A1799-1816ins BRAF mutations in papillary thyroid cancer; the two new mutations resulted in constitutive activation of the BRAF kinase and caused NIH3T3 cell transformation, Overexpression of B-Raf mRNA and protein may be a feature of nonfunctioning pituitary adenomas, highlighting overactivity of the Ras-B-Raf-MAP kinase pathway in these tumors., BRAF gene plays a "gatekeeper" role but does not act as a predisposition gene in the development of low-grade ovarian serous carcinomas, BRAFV600E represents a detectable marker in the plasma/serum from melanoma patients for monitoring but not diagnostic purposes, B-RAF mutations are a rare event in pituitary tumorigenesis., The aim of this study was to identify the effect that BRAF oncogene has on post-transcriptional regulation in papillary thyroid carcinoma by using microRNA analysis., 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., BRAF(V600E) mutation is identified in a subset of cutaneous metastases from papillary thyroid carcinomas, data suggest that BRAF mutations might be present less frequently than KRAS mutations in Greek patients with colorectal carcinomas, finding of a strong association between BRAF mutations and serrated histology in hyperplastic aberrant crypt foci supports the idea that these lesions are an early, sentinel, or a potentially initiating step on the serrated pathway to colorectal carcinoma, BRAF V600E mutation was occasionally observed in anaplastic carcinomas with papillary carcinoma., MSI is rare in UC-related neoplasia as well as non-neoplastic lesions, and does not contribute to the development of dysplasia., prevalence of BRAF mutation and RET/PTC were determined in diffuse sclerosing variant of papillary thyroid carcinoma; none of the cases showed a BRAF mutation, Molecular diagnosis and careful observations should be considered in children with Cardio-facio-cutaneous syndrome because they have germline mutations in BRAF and might develop malignancy., c-kit expression is not alternative to BRAF and/or KRAS activation., BRAF V600E mutation in PTCs is associated with reduced expression of key genes involved in iodine metabolism, 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, analysis of a BRAF mutation-associated gene expression signature in melanoma, 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, frequency of the BRAF mutation and the associations between BRAF mutation and clinicopathologic parameters in papillary thyroid carcinoma were evaluated by meta-analysis, T1790A BRAF mutation (L597Q) in childhood acute lymphoblastic leukemia is a functional oncogene, The heterogeneous distribution of BRAF mutations suggests that discrete tumor foci in multifocal PTC may occur as independent tumors., Presence of BRAF V600E in very early stages of papillary thyroid carcinoma., influence of B-RAF-specific RNA interference on the proliferation and apoptosis of gastric cancer BGC823 cell line, We conclude that screening for BRAF 15 exon mutation is an efficient tool in the diagnostic strategy for HNPCC, 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., KLF6 and p53 mutations are involved in the development of nonpolypoid colorectal carcinoma, whereas K-ras and B-raf mutations are not, PPARbeta/delta has a role in growth of RAF-induced lung adenomas, BRAF V600E mutation in papillary carcinoma of the thyroid may facilitate tumor cell growth and progression once seeded in the lymph nodes., There was no coexistence of BRAF (V600E) mutation in papillary thyroid carcinoma., data showed differences in gene expression between nevi with and without the V600E BRAF mutation. Moreover, nevi with mutations showed over-expression of genes involved in melanocytic senescence and cell cycle inhibition, RNA interference and pharmacologic approaches were used to assess the role of B-Raf activation in the growth of human melanomas and additionally determined if a similar role for mutant B-Raf is seen for colorectal carcinoma cell lines., 5 unreported mutations (T241P, Q262R, G464R, E501V, N581K) were found in cardio-facio-cutaneous syndrome. A hotspot in exon 6 at Q257 was found., diffuse expression of wild-type and/or mutant B-Raf may be involved in the tumorigenic process, BRAF V600E mutation is primarily present in conventional papillary thyroid cancer; it is associated with an aggressive tumor phenotype and higher risk of recurrent and persistent disease in patients with conventional papillary thyroid cancer, Develompment of malignant strumo ovarii with papillary thyroid carcinoma features is associated with BRAF mutations., BRAF(V600E) mutation detected on fine-needle aspiration biopsy specimens, more than RET/PTC rearrangements, is highly specific for papillary thyroid carcinoma., BRAF V600E mutation is associated with high-risk papillary thyroid carcinoma, BRAFV600E mutations were found in 41.2% of the papillary thyroid carcinomas, Papillary thyroid cancers with no 131I uptake had a high frequency of BRAF mutations., MEK inhibition is cytostatic in papillary thyroid cancer and anaplastic thyroid cancer cells bearing a BRAF mutation, effects of a MEK inhibitor, CI-1040, on thyroid cancer cells, some of which, particularly cell proliferation and tumor growth, seemed to be BRAF mutation or RAS mutation selective, BRAF mutation is associated as early as the hyperplastic polyp stage followed by microsatellite instability at the carcinoma stage, Examined associations between BRAF mutations, morphology, and apoptosis in early colorectal cancer., BRAF mutation represents a novel indicator of the progression and aggressiveness of papillary thyroid cancer (Review), BRAF interacts with PLCepsilon1 in nephrotic syndrome type 3. Both proteins are coexpressed and colocalize in developing and mature glomerular podocytes., In this small study, the T1799A BRAF mutation was identified in almost half of the iris melanoma tissues samples examined. This finding suggests that there may be genetic as well as clinical differences between iris and posterior uveal melanomas., These results suggest that papillary thyroid carcinomas with BRAF (V600E) mutation are more aggressive than those with wildtype BRAF., 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., no BRAF mutations identified in 65 screened JMML patients; this gene is unlikely to play a role in the pathogenesis of JMML., The BRAF mutation is common in melanomas, but variation in rates across melanoma subtypes points to a complex interplay between BRAF activation and other factors (eg, sun exposure)., the results of HRAS, BRAF and MAP2K1/2 mutation screening in a large cohort of patients with CS and CFC, Detection of BRAF improves the diagnosis in fine-needle biopsy with cytological findings suspicious for papillary thyroid carcinoma., These results identify Rnd3 as a regulator of cross talk between the RAF/MEK/ERK and Rho/ROCK signaling pathways, and a key contributor to oncogene-mediated reorganization of the actin cytoskeleton and focal adhesions., BRAF and MEK1/2 mutations may be more common than anticipated in ovarian cancer which could have important implications for treatment of patients with this disease and suggests potential new therapeutic avenues, BRAF(V600E)'alone' does not represent a marker for poor outcome, B-Raf(V600E) signaling deregulates the mitotic spindle checkpoint through stabilizing Mps1 levels in melanoma cells., BRAF provides proliferation and survival signals in MSI colorectal carcinoma cells displaying BRAF(V600E) but not KRAS mutations., Because of the very sensitive pyrophosphorolysis-activated polymerization (PAP)technology, B-RAF mutations were found in cell lines and primary uveal melanomas., 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., frequency of the occurrence of BRAF mutation and/or RET/PTC in H4-PTEN positive tumors was extremely high (75%) in papillary thyroid carcinoma, BRAF mutation is not associated with cutaneous melanoma, Important signalling role in T cell development., Follicular histotypes of oncocytic thyroid carcinomas do not carry BRAF mutations, Mutant B-RAF mediates resistance to anoikis via Bad and Bim., A genome-wide RNA-interference screening to identify genes required for an activated BRAF oncogene to block proliferation of fibroblasts and melanocytes revealed that a IGFBP7, has a central role in BRAF-mediated senescence and apoptosis., BRAF T1799A mutation is associated with aggressive pathological outcomes of papillary thyroid cancer, BRAF(V600E) mutation is asscoiated with papillary thyroid cancer, BRAF-V600E mutation is associated with familial non-medullary thyroid carcinoma, 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., RKIP could play an important role in the down-regulation of wild-type BRAF, serving thus as an endogenous inhibitor of the MAPK pathway in nasal polyps and their adjacent turbinate mucosa., BRAF mutation testing of papillary thyroid carcinoma might improve the diagnosis, prognostic stratification and treatment of these tumors., Our data provide evidence that PIK3CA and BRAF contribute to the tumorigenesis of IPMN/IPMC, but at a lower frequency than KRAS., This study confirms that the known MC1R-melanoma risk association is confined to subjects whose melanomas harbor BRAF mutations., BRAF mutation is associated with disease stabilization in melanoma, Thyroid cancers with BRAF mutation are preferentially sensitive to MEK inhibitors., Detecting BRAF mutation by pyrosequencing is more sensitive, faster, and less expensive than direct DNA sequencing., K-RAS and BRAF mutations are a frequent genetic event in our samples of sporadic papillary and medullary thyroid carcinoma., is commonly activated by somatic point mutation, it may provide possible diagnostic and therapeutic targets in human malignant tumors., Results implicate aberrant activation of the MAPK pathway due to gene duplication or mutation of BRAF as a molecular mechanism of pathogenesis in low-grade astrocytomas and suggest inhibition of the MAPK pathway as a potential treatment., Aberrant BRAF and INK4A functionally interact to promote growth and survival of melanoma cells., in melanocytic lesions, BRAF(V600E) mutation can affect a subset of the cells and is associated with the type and quantity of sun exposure, study describes the biochemical characterization of novel BRAF and MEK germline mutations in cardio-facio-cutaneous syndrome, Cdk1/cyclin B has a role in regulating B-raf activation at mitosis, CpG island methylator phenotype in colorectal neoplasms may result from activating mutations in either BRAF or KRAS., Akt3 and mutant V600E B-Raf cooperate to promote early melanoma development., oncogenic BRAF inhibition can have a different effect on cell fate depending on the cellular type, aberrant methylation of the hMLH1 gene may play a role in BRAF mutation-promoted thyroid tumorigenesis, study revealed a significant correlation of BRAFV600E mutation with a lower expression of both sodium iodide symporter and thyroperoxidase in papillary thyroid cancer, Shorter overall survival in primary melanoma was associated with the presence of ulceration and BRAF exon 15 mutations, as well as the absence of nuclear activation of Akt and of cytoplasmic activation of ERK., BRAF mutations in colorectal cancer microsatellite-stable cases are associated with high levels of chromosomal instability that are likely responsible for the adverse outcomes in these cases, a significant relationship in overall survival in colon cancer patients with defective DNA mismatch repair and the presence of a specific mutation in BRAF (V600E), Compared to melanomas without BRAF mutations, melanomas with BRAF mutations showed statistically significantly higher degrees of intraepidermal scatter of melanocytes, and a higher proportion of melanocytes arranged in nests., the scaffold protein IQGAP1 couples Ca(2+) and calmodulin signaling to B-Raf function, Rac1b and B-Raf(V600E) functionally cooperate to sustain colorectal cell viability and suggest they constitute an alternative survival pathway to oncogenic K-Ras, V600E BRAF mutation is associated with imatinib-resistant gastrointestinal stromal tumors, MLH1 methylation and BRAF mutations are associated with microsatellite unstable colon tumors, The frequencies of LOHs of 17q21, 17p13, 10q23, and 22q13 were higher in tumors with lymph node metastasis, suggesting that these LOHs may be important in increased lymph node metastasis., People of southern European origin had lower risk of colorectal cancers with CIMP and BRAF mutation than people of Anglo-Celtic origin, which may in part be due to genetic factors that are less common in people of southern European origin., BRAF regulates melanoma proliferation through the lineage specific factor MITF, co-overexpression of KIT/CDK4 is a potential mechanism of oncogenic transformation in some BRAF/NRAS wild-type melanomas, lung adenocarcinoma of mixed type with a high incidence of papillary and lepidic growth may be worthwhile investigating for BRAF-V600E mutation as more genetically oriented drug therapies emerge., hyperactivation of the MAPK pathway following activation of an inducible form of oncogenic C-Raf induces a senescence-like proliferation arrest in B-Raf mutant melanoma cells, N-RAS(Q61K) and B-RAF(V600E) contribute to melanoma's resistance to apoptosis in part by downregulating Bim expression, CST6, CXCL14, DHRS3, and SPP1 are regulated by BRAF signaling and may play a role in papillary thyroid carcinoma pathogenesis, The BRAF(V600E) mutation was demonstrated to be a poor prognostic factor independent from other clinicopathological features., Identification and functional characterization of a novel T599I-VKSR(600-603)del BRAF mutation in a patient with follicular variant papillary thyroid carcinoma., There is a higher frequency of the BRAF(V600E) mutation in papillary thyroid carcinomas than in normal thyroid tissue., These data suggest that regulation of BIM expression by BRAF-->MEK-->ERK signaling is one mechanism by which oncogenic BRAF(V600E) can influence the aberrant physiology of melanoma cells., focal gains at chromosome 7q34 and increased BRAF-MEK-ERK signaling are common findings in sporadic pilocytic astrocytomas, presence of the BRAF (V600E) mutation,the incidence of microsatellite instability high colorectal cancer in populations based study., KRAS and BRAF mutations can impair response to anti-EGFR therapy for colorectal neoplasms, BRAF mutation is associated with the CpG island methylator phenotype in colorectal cancer from young patients, BRAF, KRAS and PIK3CA mutations occur prior to malignant transformation demonstrating that these oncogenic alterations are primary genetic events in colorectal carcinogenesis, These data implicates a mitotic role for B-Raf in regulating spindle formation and the spindle checkpoint in human somatic cells., study identified a group of melanomas with low-activity BRAF mutations (G469E- and D594G) that are reliant upon CRAF-mediated survival activity, BRAF mutation occurs independently of CpG island methylator phenotype and MSI in all types of serrated polyps and may serve as a marker of serrated pathway of colorectal carcinogenesis, study concludes a single endogenous BRAF(V600E) allele is sufficient to repress BIM & prevent death from growth factor withdrawal; colorectal cancer cells with V600E mutations are addicted to the ERK1/2 pathway for repression of BIM, CIMP-high appears to be an independent predictor of a low colon cancer-specific mortality, while BRAF mutation is associated with a high colon cancer-specific mortality., 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., BRAF(V600E) mutation may play some roles in local carcinoma development, there is no evidence that BRAF(V600E) mutation significantly reflects the aggressive characteristics and poor prognosis of patients with papillary carcinoma in Japan., BRAF V600E appeared to be the most commonly mutated gene in both the melanocytic aggregate (seven of 18, 39%) and the melanoma (four of 18, 22%), Hereditary pancreatitis patients with PRSS1 mutations also had mutations in BRAF and KRAS2., study shows high expression of p16(INK4a) or the absence of activated B-RAF correlates with in vivo response of melanoma to cytotoxic drugs, rearrangement, which was not observed in a series of 244 higher-grade astrocytomas, results in an in-frame fusion gene incorporating the kinase domain of the BRAF oncogene, the T1799A BRAF mutation is present in a proportion of posterior uveal melanomas but within these tumours the distribution of the mutation is heterogeneous., BRAF mutations may not play an important role in the oncogenesis or therapy of prostate adenocarcinoma, 8% of sporadic colorectal tumors in this study harbor mutation in the BRAF gene., Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer., BRAF-V600E mutation is uncommon in endocrine tumors other than thyroid papillary carcinomas, The result showed that the mutation rate of PIK3CA in nasopharyngeal carcinomas (n = 73) was 9.6%, whereas both BRAF (n = 65) and RAS (n = 45) were wild type in every specimen with adequate DNA for analysis., In Korean patients with papillary thyroid carcinoma, the BRAFV600E mutation is associated with a lower frequency of background Hashimoto thyroiditis and a high frequency of lymph node metastasis., Reverse transcription polymerase chain reaction-based sequencing revealed a fusion product between KIAA1549 and BRAF in pediatric low-grade astrocytomas, ovarian cancer patients with KRAS or BRAF mutations may benefit from CI-1040 treatment, BRAF(V600E) mutation is assocciated with aggressive papillary thyroid microcarcinoma., NRAS and BRAF mutations increase from the radial to the vertical growth phase in cutaneous melanoma, Genetic extinction of BRAF(V600E) in established prostate tumors did not lead to tumor regression, indicating that while sufficient to initiate development of invasive prostate adenocarcinoma, BRAF(V600E) is not required for its maintenance., G12D mutation may be more likely selected in a BRAF mutated context, ERK activation was induced by PKD2 overexpression via B-Raf signaling, providing a possible molecular mechanism of cystogenesis, BRAF pseudogene activation may play a role in thyroid tumor development., Sessile serrated adenomas are encountered commonly in routine endoscopy practice and the histological diagnosis correlates strongly with the presence of BRAF mutation., BRAF and RET/PTC dual mutations are associated with recurrent papillary thyroid carcinoma, MLH1-hypermethylated tumors harbor fewer APC and KRAS mutations and more BRAF mutations, suggesting that they develop distinctly from an MGMT methylator pathway., Mutations are absent or rare in the kinase domain of B-RAF in Japanese head and neck squamous cell carcinoma., Mutation in BRAF is associated with adrenocortical carcinomas., Distinct BRAF (V600E) and KRAS mutations in high microsatellite instability sporadic colorectal cancer in African Americans., Expression levels of fibronectin, vimentin and CITED1 were positively correlated with those of BRAFV600E, suggesting pathophysiological links between activated BRAF and overexpression of these genes., (novel) mutation in the activation kinase domain of the BRAF (A598V), this mutation led to the up-regulation of the BRAF kinase activity and its downstream signaling factors., Findings provide evidence for a wide phenotypic diversity associated with mutations affecting BRAF, and occurrence of a clinical continuum associated with these molecular lesions., the presence of the braf protein mutation increases prohibitin promoter activity and therefore potentially mediates effects of this mutation on the behavior of BRAF protein, BRAFT1799A mutation or RET/PTC rearrangement, mainly corresponding to follicular variants, maintain a thyroid differentiation expression level close to that of normal tissue., BRAF* melanomas appear to be associated with a specific profile of DNA copy number aberrations that is distinct from those found in NRAS* and BRAF/NRAS(wt/wt) tumors., oncogenic BRAF(V600E) induces the uncoupling of LKB1-AMPKalpha complexes providing at the same time a possible mechanism in cell proliferation that engages cell growth and cell division in response to mitogenic stimuli, GDC-0879-mediated efficacy was associated strictly with BRAF(V600E) status, MEK inhibition also attenuated proliferation and tumor growth of cell lines expressing wild-type BRAF., study of KRAS/BRAF mutation status in a large and well-documented cohort of primary and metastatic renal cell carcinoma, a correlation between a gene mutation--BRAF V600E--and cisplatin resistance in nonseminomatous germ cell tumors., Both BRAF and RKIP expression levels exhibit a decrease from normal skin tissue and actinic keratosis, going to squamous cell carcinoma., In BRAF mutated colorectal carcinoma cells quercetin, luteolin and ursolic acid decreased Akt phosphorylation, BRAF(V600E) is associated some of the aggressive clinicopathological features of papillary thyroid carcinoma including younger age at diagnosis, larger tumor size, and classic histological type, as well as also extrathyroidal invasion., Targets of phosphorylation by B-Raf signaling are investigated in melanoma., 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., BRAF V600E mutation was significantly found in papillary thyroid carcinoma., Mutation in BRAF is associated with ERK1/2 activation and MEK1/2 inhibitor therapy in colorectal cancer., proliferation of cells harboring mutations in B-Raf, but not K-Ras, is exquisitely sensitive inhibition of the MAPK pathway, 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., The genes whose expression is associated with BRAF mutations are not simply restricted to the MAPK/ERK signaling but also converge to enhanced immune responsiveness, cell motility and melanosomes processing involved in the adaptative UV response, a subpopulation of melanocytes possesses the ability to survive BRAF(V600E)-induced senescence, B-RAF mutation was found to be significantly higher in papillary carcinomas when compared to follicular variant of papillary thyroid carcinomas (55.6% vs 14.3%, P = 0.05)., The murine model of mutant BRAF-induced melanoma formation provides an important tool for identifying further genetic alterations that cooperates with BRAF and that may be useful in enhancing susceptibility to BRAF-targeted therapeutics in melanoma., elevated pERK expression occurs in urothelial carcinoma in the absence of B-Raf mutations and is not correlated with FGFR3 over-expression, Investigated BRAF mutations in 30 bladder tumors. Detected two tumor specimens bearing two different mutations, both of which were found in exon 15. One sample showed the T1799A (V600E) and the other the G1798T (V600L) mutation., The T1799A BRAF mutation does not appear to play a role in the tumorigenesis of the cribriform-morular variant of papillary carcinoma., Novel BRAF mutation in a patient with LEOPARD syndrome and normal intelligence is reported., BRAF V600E mutation is not the target gene for abnormal DNA mismatch repair in patients with sporadic endometrial cancer., Report efficient molecular screening of Lynch syndrome by specific 3' promoter methylation of the MLH1 or BRAF mutation in colorectal cancer with high-frequency microsatellite instability., Mutations in BRAF were found 10% 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, mismatch repair deficiency is not a crucial event for BRAF mutation in melanocytic tumors, The RAS/RAF/MEK/ERK signaling pathway has emerged as a major player in the induction and maintenance of melanoma, particularly the protein kinase BRAF, mutated in approximately 44% of melanoma cases. Review., data confirm that KRAS and BRAF mutations do occur in the same cell and that BRAF V600E mutation is associated with CIMP+ status., B-Raf/MKK/ERK provides a permissive environment for melanoma genesis by modulating plexin B1., If BRAF is mutated in the primary thyroid neoplasm, it is likely that the metastases will harbor the defect., Targeting NRAS alone or both BRAF and CRAF in combination or both BRAF and PIK3CA together showed delay in tumor growth., Results show that activating BRAF somatic mutations may be occasionally found in advanced adrenocortical carcinomas, while CTNNB1 activating mutations are early and common events in adrenal tumorigenesis., CTNNB1 and BRAF mutations may have roles in the cribriform-morular variant of papillary thyroid carcinoma, BRAF V600E may have a role in development of papillary thyroid carcinoma, Pilocytic astrocytomas had BRAF fusions in 70% of cases but not IDH1 or IDH2 mutations. Diffuse astrocytomas had IDH1 mutations in 76% of cases but not IDH2 mutations or BRAF fusions. Analysis of BRAF and IDH1 separates pilocytic from diffuse astrocytoma., BRAF mutations represent an alternative molecular pathway in the early tumorigenesis of a subset of KIT/PDGFRA wild-type GISTs and are per se not associated with a high risk of malignancy., study concludes that a BRAF mutation is a negative prognostic marker in patients with metastatic colorectal cancer, BRAF mutated tumors occurred with a much greater frequency in proximal colon tumors than in either distal colon or rectal tumors, We observed no association between germline MC1R status and somatic BRAF mutations in melanomas, BRAF V600E mutation analysis can significantly improve FNAB diagnostic accuracy., 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., BRAF (P=0.01) mutations predicted reduced progress free survival in response to cetuximab salvage therapy in patients with metastatic colorectal cancer ., Mutated BRAF is a target in metastatic melanomas, In this study, 28 matched tumor and serum samples obtained from patients with both benign and malignant thyroid disorders were analyzed for BRAF mutation., Characterization of candidate gene copy number alterations in the 11q13 region along with BRAF and NRAS mutations in human melanoma., strong inter-relation between DR4 AND DR5 overexpression and presence of oncogenic KRAS/ BRAF mutations in colon cancer., Sorafenib inhibits NSCLC cell growth by targeting B-RAF in cells with wild-type KRAS and C-RAF in those with mutant KRAS., BRAFV600E mutation is associated with papillary thyroid carcinoma., simultaneous depletion of both MITF and BRAF(V600E) significantly inhibited melanoma growth even for the melanoma cell lines resistant to MITF depletion, Studies indicate that in pilocytic astrocytomas, the BRAF fusion gene has been identified as a specific and frequent event leading to potentially targetable mitogen-activated protein kinase pathway activation., Studies indicate that drugs are effective in targeting essential molecular pathways of BRAF, PTEN, Akt and mammalian target of rapamycin., Mutations in BRAF protein is associated with Colorectal Carcinoma., Investigated the prevalence of PTPN11, HRAS, KRAS, NRAS, BRAF, MEK1, and MEK2 mutations in a relatively large cohort of primary embryonal Rhabdomyosarcoma (RMS) tumors. No mutation was observed in BRAF and MEK genes., This study provides a basis for understanding the molecular processes that are regulated by (V600E)BRAF/MEK signalling in melanoma cells., a dual mechanism that affects the Sprouty2/B-Raf interaction, Whenever necessary BRAF testing may be performed on the residual samples of thyroid nodules, without interfering with routine cytology., The BRAF(V600E) mutation can be used as a potential prognostic factor in PTMC patients in a BRAF(V600E)-prevalent area., DGKeta acts as a novel critical regulatory component of the Ras/B-Raf/C-Raf/MEK/ERK signaling cascade via a previously unidentified mechanism., analysis of the effect on the Ras/Raf signaling pathway of post-translational modifications of neurofibromin, This article focuses on reviewing the impact of the BRAFV600E mutation in the tumorigenesis of Papillary thyroid carcinoma, EPAC-mediated cellular effects require activation of the B-Raf/ERK and mTOR signaling cascades, Insights into the molecular function of the inactivating mutations of B-Raf involving the DFG motif., Papillary carcinomas of the thyroid with papillary growth and areas of follicular growth have a high frequency of BRAF mutations., Beta-catenin nuclear labeling is a common feature of sessile serrated adenomas and correlates with early neoplastic progression after BRAF activation., The polyclonality of BRAF mutations in acquired melanocytic nevi suggests that mutation of BRAF may not be an initial event in melanocyte transformation., analysis of coexisting NRAS and BRAF mutations in primary familial melanomas with specific CDKN2A germline alterations, As predicted from the genomic organization at this locus, 22 of 36 patients with sporadic pilocytic astrocytomas and B-Raf gene rearrangement also exhibit corresponding homeodomain interacting protein kinase-2 (HIPK2) gene amplification., data argues against obligatory downregulation in IGFBP7 expression in BRAF mutated melanoma cells, BRAF(T1799A) can be detected in the blood of papillary thyroid carcinoma patients with residual or metastatic disease and may provide diagnostic information, BRAF V600E mutations were seen in 83% of proximal and 74% of distal hyperplastic colonic polyps, BRAFV600E oncogene induces transforming growth factor beta secretion leading to sodium iodide symporter repression and increased malignancy in thyroid cancer., These data demonstrate the feasibility of BRAF mutation detection in cfDNA of patients with advanced melanoma. Future studies should aim to incorporate BRAF mutation testing in cfDNA to further validate this biomarker for patient selection., Suppression of BRAF gene expression inhibited cell proliferation in cells with BRAF(V600E) mutation., Hyperactivation of BRAF-MEK signaling activates MAP2 expression in melanoma cells by two independent mechanisms, promoter demethylation or down-regulation of neuronal transcription repressor HES1., BRAF and KRAS oncogenes have different transforming capability in colon cancer, The knowledge of BRAF mutation status can facilitate more accurate risk stratification and better decision making at various steps in the management of papillary thyroid 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., 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., BRAF gene mutation is associated with colorectal cancer., BRAF mutations are not relevant for rectal carcinogenesis, Data show that melanoma cells expressing B-Raf(V600E) display a reduced C-Raf, The BRAF V600E mutational status appears to be of limited diagnostic utility in distinguishing genital naevi that exhibit atypia from those that do not., v-Raf murine sarcoma viral oncogene mutations are common in ovarian serous bordeline tumors., clinical, cytologic, and pathologic parameters of 106 consecutive surgically treated patients with BRAF-positive PTC were compared with a concurrent cohort of 100 patients with BRAF-negative PTC (papillary thyroid carcinoma), 2-fold increased risk of BRAF V600E colonic tumor mutation was observed in current and former cigarette smokers homozygous for the OGG1 polymorphism, BRAF T1796A mutation was identified in 27% of papillary thyroid cancer samples and its identification may be used to determine this risk factor of the development of papillary thyroid cancer., BRAFV600E mutation is associated with high-risk clinicopathological characteristics of papillary thyroid carcinoma and worse prognosis of patients, 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, BRAF V600E detection in the tumor does not induce a higher expression of the B-raf protein or the preferential activation of the p42/44 mitogen-activated protein kinase (MAPK) signaling pathway compared with GISTs without the BRAF mutation., CpG island methylator phenotype (CIMP)-specific inactivation of BRAF(V600E)-induced senescence and apoptosis pathways by IGFBP7 DNA hypermethylation might create a favorable context for the acquisition of BRAF(V600E) in CIMP+ colorectal cancer., no support for MC1R variants with BRAF mutation for melanoma risk, BRAF gene rearrangements were more common in cerebellar pilocytic astrocytoma than non-cerebellar tumors; clinical outcome was independent of BRAF status, BRAF mutations only in metastases is not associated with resistance to anti-EGFR treatment in primary colorectal tumors., BRAF(V600E) mutation seems to define a subset of malignant astrocytomas in children, in which there is frequent concomitant homozygous deletion of CDKN2A (five of seven cases)., 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., Data demonstrate a signaling loop between B-Raf activation and p73 function, and suggest that low expression of TAp73 in colorectal cancer cell lines with mutated B-Raf may lead to lack of response to oxaliplatin/cetuximab., BRAF activating mutations are a major genetic alteration in this histologic group of pediatric low-grade brain tumors., With MSI, specific KRAS and BRAF mutations, 3 distinct prognostic subgroups were observed, High oncogenic BRAF levels trigger autophagy, which may have a role in melanoma tumor progression., we measured the prevalence and epidemiologic correlates of the BRAF V600E somatic mutation in cases collected as a part of a population-based case-control study of colorectal cancer in northern Israel., pathogenesis of papillary thyroid cancer , and the clinical implications of BRAF(V600E) mutation in the diagnosis, prognosis and potential targeted therapeutic strategies for thyroid cancer [review], 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, BRAF mutation is not associated with interval cancers but is a marker of poor prognosis, particularly in microsatellite stable cancers., Our study suggests that mutations of KRAS, not BRAF, may play a role in the pathogenesis of prostate carcinoma in Chinese patients., Studies show FOXD3 is suppressed by B-RAF, uncover a novel role and mechanism for FOXD3 as a negative cell cycle regulator, and have implications for the repression of melanocytic lineage cells., Mutated in melanoma., The miR-146b expression levels in papillary thyroid carcinoma with BRAF mutation were significantly higher than those without this mutation, Activated Raf-1 induces focal adhesion kinase expression and regulates neuroendocrine and metastatic phenotypes in gastrointestinal carcinoid cell line BON., thyroid carcinoma with the BRAF(V600E) mutation tends to be taller than wide and is not associated with the presence of calcifications on ultrasound., B-RAF(V600E) can protect melanocytes from anoikis independently of cell cycle inhibition, This study identified an exceptionally high frequency of KIAA1549-BRAF fusions in pilocytic astrocytoma., These data demonstrate a high prevalence of B-RAF mutations in the present study population, underscoring the possibility of strong regional differences., Hypoxia-inducible factor-1alpha is expressed in papillary thyroid carcinomas and is regulated not only by hypoxia but also by BRAF(V600E)-mediated signaling pathway., Study concludes that the secreted protein IGFBP7 is dispensable for B-RAF(V600E)-induced senescence in human melanocytes., BRAF V600E mutations are associated with MSI-H status and cyclin D1 overexpression and characterize a subgroup of patients with poor prognosis., Knockdown of B-Raf(V600E) resulted in thrombospondin-1 down-regulation and a reduction of adhesion and migration/invasion of human thyroid cancer cells., The V600E BRAF mutation confers a worse prognosis to stage II and stage III colon cancer patients independently of disease stage and therapy., BRAF mutation may be used a biomarker for the selection of patients with colorectal cancer patients who might benefit from anti-egf receptor monoclonal antibodies., Studies identified the oncogenic BRAF V600E mutation in 35 of 61 archived specimens (57%)., The BRAF 1799T>A mutation was found in 5 of 19 (26%) of infiltrative follicular variant of papillary thyroid carcinomas and in none of the encapsulated carcinomas, HER2, but not EGFR gene amplification, is frequently observed in KRAS and BRAF wild type colorectal cancer patients, reports the low frequency of PIK3CA and B-RAF mutations in astrocytomas, despite the presence of activated ERK and AKT proteins, Incidence of cancer in FDRs of index CRC patients with the p.V600E BRAF mutation may be explained by a genetic predisposition to develop cancer through the serrated pathway of colorectal carcinogenesis., PIK3CA mutations may have a role in KRAS and BRAF wild type colorectal cancer, BRAF mutational status of metastases is not required when the primary tumour is BRAF wild type., allele specific Taqman-based real-time PCR assay allows the sensitive, accurate and reliable measurement of BRAF(V600E) mutated DNA in plasma, in melanomas activation of the MAPK pathway can occur through signaling pathways operating independently of BRAF T1799A, V600E BRAF mutation is not associated with seminoma., Using traditional PCR and direct sequencing, we found KRAS mutations in 47 (40%) patients and BRAF(V600E) in 10 (8.5%), 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., PCR is practically applicable to KRAS/BRAF genotyping using small amounts of biopsied colorectal tumor cells., No significant difference in BRAF alterations was found between pT1 tumors and thyroid capsule invasion and pT3 tumors., 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 delineate how mutant B-RAF protects melanoma cells from apoptosis and provide insight into possible resistance mechanisms to B-RAF inhibitors., Traditional DNA sequencing and the somewhat more-sensitive pyrosequencing method can detect multiple alternative BRAF mutations., Mutant Braf can be detected in RNA from mixed populations with as few as 0.1% Braf(V600E) mutant cells., PLX4032 has robust activity in BRAF mutated melanoma., association between MC1 receptor germline variation and BRAF/NRAS mutations in melanoma, BRAF mutation is rare in advanced-stage low-grade ovarian serous carcinomas., Mutant protein kinase elicits significant therapeutic responses in mutant BRAF-driven human melanoma xenografts., first report implicating BRAF mutation in OSCC. study supports that mutations in the BRAF gene makes at least a minor contribution to OSCC tumorigenesis., BRAF mutation detection in fine needle biopsy may be an adjunct tool for preoperative didagnosis of papillary thyroid carcinoma., RET rearrangements and BRAF mutation in undifferentiated thyroid carcinomas having papillary carcinoma components, A BRAF aberrant splice variant with an intact kinase domain and partial loss of the N-terminal autoinhibitory domain was identified in fibroblasts from an additional patient, and fibroblast proliferation was inhibited by BRAF-specific siRNA., reduced RKIP mRNA levels and the elevated levels of B-RAF in pT1, grade III tumors vs. normal tissue, corroborate that these genes are involved in the pathogenesis of urinary bladder cancer., BRAF V600E mutation is associated with lack of response in wild-type KRAS metastatic colorectal cancer treated with anti-EGFR monoclonal antibodies., Determination of the BRAF mutation and the growth fraction of melanomas may add a prognostic value., BRAF(V600E) mutation is associated with thyroid nodules., In the present series, no BRAF mutation was detected. 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., BRAF is mutated in a low percentage of follicular variant of papillary thyroid carcinoma, and most of these mutated cases are suspicious or positive on fine-needle aspiration., BRAF mutation is associated with papillary thyroid microcarcinoma., Anti-BRAF autoantibodies from RA patients preferentially recognize one BRAF peptide, Braf mutation is associated with basal and treatment-induced regulation of the PI3K-AKT pathway as a critical regulator of AZD6244 sensitivity in cutaneous melanoma., Describe benign serrated colorectal fibroblastic polyps/intramucosal perineuriomas are true mixed epithelial-stromal polyps (hybrid hyperplastic polyp/mucosal perineurioma) with frequent BRAF mutations., Although many studies document BRAF mutation as a prognostic factor in PTC our results underline that it is too early to consider it as a routine clinical predictive factor., findings indicate that somatic mutations in KRAS and PIK3CA but not BRAF oncogenes are closely associated with the development of cholangiocarcinoma in Chinese population, The dermoscopical and histopathological patterns of nevi correlate with the frequency of BRAF mutations., Data show that BRAF knockdown led to suppression of the expression of the GABPbeta, which involved in regulating HPR1 promoter activity., BRAF gene amplification can promote acquired resistance to MEK inhibitors in cancer cells harboring the BRAF V600E mutation., Mutations of EGFR, BRAF, and KRAS in adenocarcinoma were mutually exclusive and inversely correlated with RASSF1A methylation, We show a strong association between concordant methylation of >/= 3 of five 3p22 genes with the CpG island methylator phenotype and the BRAF V600E mutation., 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%)., identification of MAP3K8 (the gene encoding COT/Tpl2) as a MAPK pathway agonist that drives resistance to RAF inhibition in B-RAF(V600E) cell lines, 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, It therefore appears that BRAF mutations may play a strong negative prognostic role and only a slight role in resistance to anti-EGFR Abs., Primary esophageal melanomas of Caucasian patients harbor mutations of c-Kit, KRAS and BRAF in varied frequencies., BRAF mutation in papillary thyroid carcinoma is associated with an increased risk of palpable nodal recurrence and the need for reoperative surgery., BRAF mutations activate the mitogen-activated protein kinase pathway and confer an aggressive thyroid cancer phenotype., KRAS mutations arise more frequently than BRAF mutations in Moroccan patients with colorectal carcinomas., The BRAF mutation was frequently detected in patients with superficial spreading melanoma (OR=2.021; P<0.001) and in melanomas arising in nonchronic sun-damaged skin (OR=2.043; P=0.001)., concluded that follicular variant of papillary thyroid carcinoma differs from conventional papillary thyroid carcinoma in the rate of BRAF mutation, These results show that melanoma cell phenotype is an important factor in MAPK pathway inhibition response, as invasive phenotype cell response is dependent on BRAF mutation status., this study has confirmed that the BRAF(T1799A) mutation confers cancer cells sensitivity to PLX4032 and demonstrated its specific potential as an effective and BRAF(T1799A) mutation-selective therapeutic agent for thyroid cancer., B-Raf(insT) and B-Raf(V600E) , but not B-Raf(wt) , provoke drastic morphological alterations in human astrocytes., BRAF alternative splicing is differentially regulated in human and mouse. BRAF exon 9b is required for learning and memory associated with the hippocampus., In melanoma cells, oncogenic (V600E) BRAF signaling downregulates PDE5A through the transcription factor BRN2, leading to increased cGMP and Ca2+ and the induction of invasion through increased cell contractility., B-Raf signaling has a key function in the altered expression of contractile receptors in the cerebrovasculature., The high expression of activated ERK is not caused by BRAF gene mutation in nasal mucosa malignant melanomas., Acquisition of a BRAF mutation is not a founder event, but may be one of the multiple clonal events in melanoma development, which is selected for during the progression., We found that performing BRAF(V600E) mutation analysis on the fine-needle aspiration biopsy specimens was of great help to make a therapeutic decision for thyroid nodules when the fine-needle aspiration biopsy results were equivocal, the oncogenic effect of BRAF(V600E) is associated with the inhibition of MST1 tumor suppressor pathways, and the activity of RASSF1A-MST1-FoxO3 pathways determines the phenotypes of BRAF(V600E) tumors., These findings suggest that BRAF mutations may be associated with the pathogenesis of sessile serrated colorectal adenomas., Findings suggest inhibition of autophagy in combination with ER stress-inducing agents may represent a means by which to harness autophagy for the therapeutic benefit of B-RAF wild-type melanoma., B-Raf mutations, microsatellite instability and p53 protein expression is not associated with sporadic basal cell carcinomas., The analysis of BRAF V600E mutation in 1,320 nervous system tumors reveals high mutation frequencies in pleomorphic xanthoastrocytoma, ganglioglioma and extra-cerebellar pilocytic astrocytoma., Presence of mutated BRAF is one of the most powerful prognostic factors for advanced and recurrent CRC, 803 metastatic colorectal cancer samples studied for KRAS exon 2 and BRAF exon 15 mutations; BRAF mutated samples were characterized for mismatch repair function; 344 tumours were mutated -34 involving BRAF mutations (8 of microsatellite instability type), Ras/Raf/MAPK and RhoA/ROCKII signalling pathways are abnormally activated in eutopic endometrial stromal cells of patients with endometriosis, 78 colorectal tumor samples were mutant for BRAF., analysis of gallbladder carcinomas, gallbladder adenomas, and high-grade dysplastic lesions for the BRAF and the KRAS mutations, Findings suggest that inhibition of Raf-MEK-Erk pathway might offer a novel therapeutic strategy in neuroendocrine tumors, Studies showed that siRNA knockdown of BIM significantly blunted the apoptotic response in PTEN+ melanoma cells., identified BAD serine 134 to be strongly involved in survival signaling of B-RAF-V600E-containing tumor cells and found that phosphorylation of BAD at this residue is critical for efficient proliferation in these cells., identifying downstream events from the BRAFV600E/ERK1/2 pathway will eventually identify novel biomarkers that can be used to correlate with disease outcome and overall survival., Data show that BRAF-mutated melanomas occur in a younger age group on skin without marked solar elastosis and less frequently affect the head and neck area, compared to melanomas without BRAF mutations., BRAF mutations have a smaller role in the carcinogenesis of malignant melanoma in Chinese Han than in Western patients., BRAF mutations were rare in colorectal laterally-spreading tumors., The presence of mutant BRAF had no impact on the disease-free interval from diagnosis of first-ever melanoma to first distant metastasis; however, it may have impacted survival thereafter., B-Raf associates with and stimulates NHE1 activity and that B-Raf(V600E) also increases NHE1 activity that raises intracellular pH., BRAF mutation is associated with selective inhibition of thyroid cancer cells by the novel MEK inhibitor RDEA119 and genetic-potentiated synergism with the mTOR inhibitor temsirolimus, IDH1 mutation works with other oncogenic mutations and could contribute to the metastasis in melanoma., Regulation of NR4A nuclear receptor expression by oncogenic BRAF in melanoma cells., BRAF mutational status yielded no useful prognostic information in predicting recurrence and benefits from adjuvant chemotherapy in colorectal cancer., Thus, MEK1(C121S) or functionally similar mutations are predicted to confer drug resistance of neoplasms to combined MEK/RAF inhibition., tumor initiation by oncogenic BRAF renders thyroid cells susceptible to TGFbeta-induced epithelial-mesenchymal transition, through a MAPK-dependent process, 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., 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., BRAF mutation is associated with papillary thyroid cancer., study suggested that both KRAS and BRAF mutations are exclusive, but KRAS and PIK3CA mutations are coexistent, This study demonistrated that the role of RAF kinase fusions as a central oncogenic mechanism in the development of pilocytic astrocytoma., Mutations at the position V600 of BRAF were described in approximately 8% of all solid tumors, including 50% of melanomas, 30 to 70% of papillary thyroid carcinomas and 5 to 8% of colorectal adenocarcinomas., There were no significant differences in the frequency of BRAF mutations among lesions exhibiting the hyperplastic, adenomatous, or mixed patterns., The presence of the BRAF(V600E) mutation may play different roles between medium and giant CMNs in melanocytic tumorigenesis., BRAF T1799A mutation may be an early and essential carcinogenic event in nearly all Korean papillary thyroid carcinomas, In papilary thyroid carcinoma, the BRAFT1799A mutation is associated with age over 60 & a tumor size of 1cm or greater, but not with other clinicopathological characteristics, tumor recurrence or persistence., KSR interacts with a regulatory Raf molecule in cis to induce a conformational switch of MEK, facilitating MEK's phosphorylation by a separate catalytic Raf molecule in trans, Amplification of the driving oncogene, KRAS or BRAF, underpins acquired resistance to MEK1/2 inhibitors in colorectal cancer cells., Activated BRAF promotes melanoma cell growth by matrix metalloproteinase-1, No V600E mutation was identified in the BRAF gene in any sample., the impact of BRAF mutation and microsatellite instability on prognosis in metastatic colorectal cancer, BRAF mutations are specific for serrated adenocarcinoma and identify a subset of serrated adenocarcinomas with gene methylation and a tendency for MSI-H, BRAF V600E mutations are common in the majority of pleomorphic xanthoastrocytoma., Heterogeneity of KRAS and BRAF mutation status intra-tumorally in colorectal cancer was assessed., findings support the notion that BRAF(V600E), which can be detected preoperatively in papillary thyroid carcinoma fine-needle aspiration biopsy material, has a potential to contribute to patients stratification into high- and low-risk groups., Mutated BRAF is detected in approximately 45% of papillary thyroid carcinomas (PTC)., Ablation of B-Raf had no significant effect on development of K-Ras oncogene-driven non-small cell lung carcinoma., BRAF mutations, but not KRAS mutations, were associated with a worse outcome in Chinese colorectal cancer patients., MSS/BRAF mutant cancers were more commonly proximal (38/54, 70.3%)., Analysis showed that blood samples with PCR evidence for CMC were heterogeneous for BRAF status under limiting-dilution conditions, suggestive of heterogeneity of CMC, Studies indicate that Raf kinases are excellent molecular targets for anticancer therapy., Wnt5a methylation was strongly associated with tumour microsatellite instability tumours after adjustment for age, sex, and tumour location and with BRAF V600E mutation, a marker of CpG island methylator phenotype, BRAF V600E mutation is associated with recurrent papillary thyroid cancer., introduction of constitutively active BRAF V600E into human cortical stem and progenitor cells initially promotes clonogenic growth in soft agar but ultimately results in dramatically reduced proliferation and arrested growth of the culture., Compared with BRAF-wt papillary thyroid cancer, those harboring BRAF(V600E) exhibit downregulated VEGFA, VEGFR, and PDGFRbeta expression, suggesting presence of BRAF mutation does not imply stronger response to drugs targeting VEGF and PDGFB signal pathways., The BRAF V600E mutation was present in all patients with hairy-cell leukemia who were evaluated., The BRAF V600E mutation did not show association with clinical or molecular characteristics of colorectal cancer., Eight of 16 primary tumor samples and 4 of 6 metastatic samples showed BRAF V600E gene mutations and no copy number changes were associated exclusively with metastatic cancer, The frequency of BRAF-KIAA1549 fusion transcripts is significantly lower in adult patients with pilocytic astrocytoma., MEK1(F129L) mutation also strengthened binding to c-Raf, suggesting an underlying mechanism of higher intrinsic kinase activity, The application of BRAF(V600E) mutation analysis in US-guided FNAB can improve the diagnostic accuracy of thyroid nodules., We describe a new mutation of BRAF, T599dup, in a case of anaplastic thyroid carcinoma with tall cell papillary thyroid carcinomas component., identified concurrent mutational inactivation of the PTEN and RB1 tumor suppressors as a mechanism for loss of BRAF/MEK dependence in melanomas harboring (V600E)BRAF mutations, BRAF mutation of papillary thyroid carcinoma may have differential predictive values for LN metastasis, according to tumor size., BRAF(V600E) mutation analysis using residual liquid-based preparation cytologic samples is, therefore, a powerful additional diagnostic tool for diagnosis of papillary thyroid carcinoma., 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., Importance of infiltrative growth pattern and invasiveness over presence of BRAF mutation in classic and follicular variant papillary thyroid carcinoma for development of nodal metastases., BRAF mutation is not indicative for predicting papillary thyroid cancer prognosis., study reports that V600E and non-V600E BRAF mutations affect different patients with non-small-cell lung cancer; V600E mutations are significantly associated with female sex and represent a negative prognostic factor, BRAF mutations and llelic loss of susceptibility loci are associated with familial non-medullary thyroid cancer., The BRAF/MEK/ERK pathway is upregulated in progressive retinal arterial macroaneurysm patients, caused by mutation in IGFBP7., Braf mutation in metastatic melanoma treated with BRAF inhibitor vemurafenib., Genetic analysis revealed individual heterozygous mutations in the KRAS (phenotype of CFC/Noonan syndrome) and BRAF genes (phenotype of CFC syndrome), BRAF V600E mutation has a significant correlation with papillary thyroid carcinomas., the BRAF(V600E) mutation should be considered as a poor prognostic marker in papillary thyroid cancer (Meta-Analysis), Studies indicate that BRAF V600E mutation initiates follicular cell transformation., 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%)., BRAF(V600E) causes upregulation of TIMP-1 via NF-kappaB. TIMP-1 binds then its surface receptor CD63, leading eventually to Akt activation, which in turn confers antiapoptotic behavior and promotion of cell invasion., BRAF mutations are of pathogenetic significance in wild type gastrointestinal stromal tumors., CXCR4 expression and BRAF mutation status could cooperatively induce and promote a more aggressive phenotype in papillary thyroid carcinoma through several pathways and specifically increase the tumors' spread outside of the thyroid gland., Aberrant CIMP was detected in 16% of chromosomal instable tumors and in 44% of both microsatellite instable and microsatellite and chromosomally stable carcinomas, this novel B-Raf fusion protein (SND-1 was identified as the B-Raf fusion partner) presents a novel target with potential clinical implications in the treatment of patients resistant to c-Met inhibitors., A prominent epigenetic mechanism through which BRAF V600E can promote papillary thyroid cancer tumorigenesis by altering the methylation and hence the expression of numerous important genes., BRAF mutation V600E significantly induces cell migration and invasion properties in vitro in colon cancer cells, In malignant FNABs in papillary thyroid carcinoma, BRAF(V600E) mutation was significantly associated with presence of extra-thyroidal extension and metastases after surgery., 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, An integrated approach combining both VE1 mutant protein immunohistochemistry and genetic analysis may increase the diagnostic accuracy of BRAF mutation analysis., Postmenopausal hormone therapy was associated with borderline statistically significant risk reductions for BRAF-wildtype tumours among women with prolonged exposure to Postmenopausal hormone therapy., BRAF V600E mutation is associated with hairy cell leukemia and B-cell neoplasms, high prevalence of BRAF (V600E) mutation is associated with synchronous bilateral papillary thyroid carcinoma., Results support evaluation of BRAF(V600E)-specific inhibitors for treating BRAF(V600E) malignant astrocytomas (MA) patients., study examined the clinical characteristics and outcomes of patients with mutant BRAF advanced cancer; conclude that BRAF appears to be a druggable mutation that also defines subgroups of patients with phenotypic overlap, albeit with differences that correlate with histology or site of mutation, 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], Ras induces DR5 expression through co-activation of ERK/RSK and JNK signaling pathways, BRAF V600E mutation is associated with hairy cell leukemia and other mature B-cell neoplasms, BAG3 protein sustains anaplastic thyroid tumor growth in vitro and in vivo. The underlying molecular mechanism appears to rely on BAG3 binding to BRAF, thus protecting it from proteasome-dependent degradation., Murine thyroid tumors carrying the human BRAF(V600E) mutations are exquisitely dependent on the oncoprotein for viability., BRAF (V600E) is a prevalent genetic alteration in adult sporadic papillary thyroid carcinoma in Indian cohort and it may be responsible for the progression of its classic variant., Overall, no difference existed in microsatellite instability or BRAF mutation frequencies between African Americans and Caucasians with colorectal neoplasms., BRAF mutations are associated with hairy cell leukemia and related lymphoproliferative disorders., Case Report, thieno[2,3-d]pyrimidines are B-Raf inhibitors, Pyrosequencing of BRAF V600E in routine samples of hairy cell leukaemia identifies CD5+ variant hairy cell leukaemia that lacks V600E., V600E mutation of the BRAF gene reported to be associated with poor prognosis of germ cell tumors in adults prognostic biomarkers cannot necessarily be transferred from one age group to the other., BRAF mutation is associated with inferior survival in stage III colon cancer., papillary thyroid cancers in young patients display a low prevalence of the already identified oncogenic alterations; the increasing prevalence with age is mainly due to V600E BRAF mutation, The BRAF V600E mutation is associated with a higher pathological stage at surgery and a higher rate of recurrence., BRAF mutations enhance the predictability of malignancy in thyroid follicular lesions of undetermined significance., BRAF and KRAS mutations were observed in six (46.2%) and four (30.3%) filiform serrated adenomaS, respectively., BRAF mutation in papillary thyroid carcinoma is a later subclonal event, its intratumoral heterogeneity may hamper the efficacy of targeted pharmacotherapy, and its association with a more aggressive disease should be reevaluated., The antibody response against the catalytic domain of BRAF is not specific for rheumatoid arthritis., Report mutations in KRAS, EGFR, and BRAF in cholangiocarcinoma and identify therapeutic targets for tyrosine kinase inhibitors., Findings suggest that the BRAF inhibitor vemurafenib in combination with standard-of-care or novel targeted therapies may lead to enhanced and sustained clinical antitumor efficacy in CRCs harboring the BRAF(V600E) mutation., Aberrant gene methylation driven by BRAF(V600E) altered expression of the DNA methyltransferase 1 and histone methyltransferase EZH2 profoundly., The BRAF(V600E) mutation was associated with high-risk clinicopathologic characteristics in patients with papillary thyroid cancer (PTC). The BRAF(V600E) mutation may be a potential prognostic factor in PTC patients., B-Raf gene mutation primarily occurs at two loci--the exon 11 glycine loop and the activation area of exon 15--in surgically resected specimens of hepatocellular carcinoma patients., These data support a model where the continuous regenerative process initiated by oncogenic B-RAF-driven alveolar disruption provides a tumor-promoting environment associated with chronic inflammation., 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, analysis of BRAF gene mutations in non-small cell lung cancer, These results provide a functional link between oncogenic BRAF and angiogenesis., Patients with microsatellite instability tumor phenotype had favorable prognosis, but in those with the V600E BRAF mutation higher recurrence rate was observed., Our results suggest that HCLv and IGHV4-34(+) HCLs have a different pathogenesis than HCLc and that a significant minority of other HCLc are also wild-type for BRAF V600., Although it constitutes a poor prognostic factor in colorectal cancer, it is not conclusive if it interferes with a poor therapeutic effect when cetuximab is used.[review], The findings show mutant BRAF-induced oncogenic stress manifests itself by DNA damage and growth arrest by activating the pCHK2-p53-p21 pathway.It also confers tumor-promoting phenotypes such as the up-regulation of GLUT1 and enhances glucose metabolism., In patients with colorectal adenocarcinoma, there were significant differences between BRAF wild-type and mutant tumors in age, female sex, proximal tumor location, frequency of microsatellite instability, and survival., One chronic lymphocytic leukaemia patient and one patient with B-prolymphocytic leukaemia were found to harbour the BRAF V600E mutation, Sessile serrated adenomas are precursors of sporadic colorectal cancers with microsatellite instability.Identified a novel surface microstructure, the Type II open-shape pit pattern (Type II-O), which was specific to SSAs with BRAF mutation and CIMP., evidence for heterogeneity of the BRAF(V600E) mutation within individual melanoma tumor specimens, No BRAF mutations were found in colon adenocarcinomas from renal transplant recipients., BRAF V600E mutation in low and intermediate grade lymphomas is associated with frequent occurrence in hairy cell leukaemia., None of the molecular marker mutations that were analyzed in this study, including the BRAF mutation, predicted lymph node metastasis in classic papillary thyroid carcinoma., During therapy with selective BRAF inhibitors, panniculitis with arthralgia represents a new adverse effect that can require dose reduction., Mutational activation of both BRAF and PIK3CA genes does contribute to hepatocellular tumorigenesis at somatic level in Southern Italian population., In naive GISTs carrying activating mutations in KIT or PDGFRA a concomitant activating mutation was detected in KRAS (5%) or BRAF (about 2%) genes. I, BRAF mutation is associated with colorectal serrated adenocarcinoma., No hotspot mutations in Braf were found in oral squamous cell carcinoma in a Greek population., Colon adenocarcinomas with BRAF mutations have morphologic characteristics distinct from those with KRAS mutations and BRAF-mutated proximal colonic adenocarcinomas with proficient DNA mismatch repair have an aggressive clinical course., 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., BRAFmut as a useful marker in hairy cell leukemia., BRAF mutation is an independent prognostic biomarker for colorectal liver metastasectomy., BRAF V600E mutation-positive papillary thyroid carcinomas (PTCs) displayed infiltrative growth, stromal fibrosis, psammoma bodies, plump eosinophilic tumour cells, and classic fully developed nuclear features of PTC., Data suggest that the BRAF V600E mutation does not seem to play a role in myeloid malignant transformation., (BRAF(V600E))detected in 141/170 malignant thyroid nodules (82.9%) (140 PTCs and one follicular variant of PTC). BRAF status not associated with US features with the exception of a negative relation between BRAF(V600E) and an irregular shape (p = 0.004)., This is the first reported study of the relationship between CK20/CK7 immunophenotype, BRAF mutations and microsatellite status in colorectal carcinomas, A distinct subset of atypical Spitz tumors is characterized by BRAF mutation and loss of BAP1 expression., review demonstrates that tumour BRAF V600E mutation, and MLH1 promoter 'C region' methylation specifically, are strong predictors of negative MMR mutation status[review], The presence of activating GNAS mutations, in association with KRAS or BRAF mutations, is a characteristic genetic feature of colorectal villous adenoma., evidence presented that ERK activation occurs in a K-ras or B-raf -independent manner in the majority of primary colon cancer cases; B-raf mutations are not associated with mismatch-repair deficiency through loss of hMLH1 or hMSH2 expression, The V600E BRAF mutation in papillary thyroid carcinomas may contribute to the initiation of the glycolytic phenotype and confers growth advantages in cancer, Eleven patients displayed Durable Disease Control (DDC) of which 55% had BRAF-V600E mutation positive tumors and 45% did not., Patient diagnosed with colon cancer shows poor prognosis with BRAF genetic mutation., findings show (V600E)B-RAF copy-number gain as a mechanism of acquired B-RAF inhibitor resistance in 4 out of 20 patients treated with B-RAF inhibitor, In a cohort of Indian patients with ulcerative colitis, with or without neoplasia, none showed the BRAF mutation., we have analyzed the prevalence of somatic mutations in the FGFR3, PIK3CA, AKT1, KRAS, HRAS, and BRAF genes in bladder cancers, 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., genetic association studies in population in Turkey, Investigation the prevalence of mutations in the BRAF gene and its correlation with demographic characteristics, tumor location and stage in 100 colorectal carcinoma patients from India., Article reviews the current understanding of BRAF gene, its structure, expression, and signal pathway in non-small cell lung cancer. [Review], The prevalence of EGFR, KRAS, BRAF and PIK3CA somatic mutations in 861 randomly selected Chinese patients with non-small cell lung cancer, We propose that , and that persistent phosphorylation of Mps1 through BRAF(V600E) signaling is a key event in disrupting the control of centrosome duplication and chromosome stability that may contribute to tumorigenesis., expression of these oncogenes markedly stimulated ERK1/2 activities and morphologically transformed IECs. Importantly however, Effective use of PDT in the treatment of BRAF inhibitor-associated KAs and SCCs., EFVPTC 1 patient BRAFV600E mutation, NVPTC 2 patients, FVPTC 2 patients., analysis of a patient with pancreatic metastasis arising from a BRAF(V600E)-positive papillary thyroid cancer [case report], The BRAF(V600E) mutation analysis from FNA specimens for calcified thyroid nodules may be performed for a greater negative predictive value and unveil the malignancy in 25% of indeterminate or nondiagnostic cytology., Report marked differences in the genetic pattern of the BRAF or NRAS mutated and wild-type melanoma subgroups., BRAF mutations play a limited role in the development of sinonasal cancer., Out of 1041 Korean patients with papillary thyroid carcinoma, 0.4% had rare types of BRAF mutation and three new somatic mutations were identified, An update on malignancies displaying high frequencies of BRAF mutations and the mechanisms underlying the side effects and drug resistance phenomena associated with Raf inhibitors., prevalence of the BRAF(V600E) mutation increased with increased tumor size, BRAF V600E is associated with gliomas., No BRAF V600E mutations were indentified in this study of patients with endometrial cancer., Highly sensitive and specific molecular assays such as MEMO sequencing are optimal for detecting the BRAF mutations in thyroid FNAC because these techniques can detect PTC that might be missed by cytology or less sensitive molecular assays., The (600DLAT)B-RAF and (V600E)B-RAF mutations were found enriched in DNA and mRNA from the CD1a+ fraction of granuloma., The analysis of BRAF mutations by pyrosequencing is useful to refine the risk stratification of patients with papillary thyroid carcinoma., Patients with serrated polyposis syndrome referred to genetics clinics had a pan-colonic disease with a high polyp burden and a high rate of BRAF mutation., It was shown that the dimer interface within the kinase domain plays a pivotal role for the activity of B-Raf and several of its gain-of-function mutants., The tumor with T1799A BRAF mutation and tumor sizes of 2 cm or more were clinicopathologic parameters associated with lower STAT1 activity., BRAF V600E is common in patients with low-risk papillary thyroid carcinoma but does not predict recurrence., Mutation BRAF transforms cells through cross talk with developmental pathways Hedgehog and Wnt, as well as by deregulation of colorectal cancer related kinase pathways., Report upregulation of Bim and the splicing factor SRp55 in melanoma cells from patients treated with selective BRAF inhibitors., In signet ring cell carcinoma, BRAF V600E mutation adversely affects survival in microsatellite-stable tumors, but not in high-level microsatellite-unstable tumor, study concludes that generally, overweight increases the risk of colorectal cancer; taller individuals have an increased risk of developing a tumour with a BRAF mutation or microsatellite instability, Demonstrate that BRAF V600E mutation-specific antibody can be used in immunohistochemical diagnosis of hairy cell leukemia., BRAF and KIT mutations have been found in Japanese melanoma patients., study shows there are clinically and biologically distinct subtypes of BRAF-mutant metastatic melanoma, defined by genotype, with distinct etiology and behavior; cumulative sun-induced damage in primary cutaneous melanoma and older age are associated with V600K BRAF mutations;it establishes prevalence of the BRAF mutation by age-decade, The diagnostic sensitivity for thyroid cancer is significantly increased by BRAF V600E mutation analysis, indicating that the screening for BRAF mutation in FNAB samples has a relevant diagnostic potential., Recurrent/persistent PTC in the central compartment typically harbors the BRAF mutation, abrogation of BRAFV600E-induced senescence contributes to melanomagenesis., The mTOR pathway could be a good target to enhance therapy effects in certain types of thyroid carcinoma, namely in those harboring the BRAF(V600E) mutation., These results suggest that low-grade diffuse gliomas with 1p/19q loss have frequent BRAF gains, KRAS, BRAF, and PIK3CA mutations in colorectal cancer have sustained prevalence rate in the Taiwanese population., BRAF regulates expression of long noncoding RNAs in melanocytes and melanoma cells, 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., Our results suggest that in a small fraction of diffuse gliomas, KIAA1549-BRAF fusion gene and BRAF(v600E) mutation may be responsible for deregulation of the Ras-RAF-ERK signaling pathway, Immunohistochemical detection of the mutated V600E BRAF protein in papillary thyroid carcinoma may facilitate mutational analysis in the clinical setting., BRAF p.Val600Lys mutations were present at a relatively high frequency in the cohort of metastatic melanoma patients (27/183, 15%), BRAF/NRAS mutations were identified in 58% of primary melanomas (43% BRAF; 15% NRAS), Data show that RNF149 (RING finger protein 149) interacts with wild-type BRAF., Data suggest that BRAF V600E mutation may not be widespread in hematologic malignancies, excluding hairy-cell leukemia (HCL)., Patient's BRAF mutation was likely responsible for his tumor's marked response to dasatinib, suggesting that tumors bearing kinase-impaired BRAF mutations may be exquisitely sensitive to dasatinib., BRAFV600E mutation is associated with lymph node metastasis in multiple papillary thyroid carcinoma., The presence of BRAF mutations in these adenomatous precursors to colon cancer suggests that they represent sessile serrated adenomas with complete cytologic dysplasia., In papillary thyroid cancer, significant correlations between the methylation status of four genes (TIMP3, RASSF1A, RARbeta2 and DCC) and the V600E BRAF mutation were found., Data indicate that 14% with pancreatic ductal adenocarcinomas (PDACs) and 7% ampullary adenocarcinomas (A-ACs) had mutations in both KRAS and BRAF., In papillary thyroid carcinoma BRAFV600E is associated with increased expression of the urokinase plasminogen activator and its cognate receptor, but not with disease-free interval., Hairy cell leukemia cell lines expressing annexin A1 and displaying B-cell receptor signals characteristic of primary tumor cells lack the signature BRAF mutation to reveal unrepresentative origins., 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., BRAF V600E mutations are present in approximately 90% of all kidney metanephric adenoma cases, serving as a potential valuable diagnostic tool in the differential diagnosis., Reactivation of mitogen-activated protein kinase (MAPK) pathway by FGF receptor 3 (FGFR3)/Ras mediates resistance to vemurafenib in human B-RAF V600E mutant melanoma., BRAF V600E mutation revealed a strong association with specific histological variants of papillary thyroid carcinoma., These results clearly prove that the BRAFV600E mutation is not associated with the development of distant metastases or fatal outcome in papillary thyroid carcinoma, Vemurafenib is effective for advanced melanomas expressing the BRAF V600E mutations [review], BRAF V600E mutation is associated with response to vemurafenib in lung adenocarcinoma., B-Raf/MKK/ERK controls key aspects of cancer cell behavior and gene expression by modulating a network of miRNAs with cross-regulatory functions., study reports a novel complex BRAF mutation identified in 4/492 Japanese papillary thyroid carcinoma(PTC) cases; findings suggest the BRAF(V600delinsYM)mutation, is a gain-of-function mutation and plays an important role in PTC development, study found a relatively higher B-Raf serine/threonine-protein kinase (BRAF)(V600E) mutation rate in classical type papillary thyroid carcinomas than in other similar studies, BRAF mRNA expression may help to identify PTC among thyroid nodules independently of the presence of BRAFV600E mutation., BRAF (V600) mutations are are associated with melanomas., Lung cancers with acquired resistance to EGFR inhibitors occasionally harbor BRAF gene mutations but lack mutations in KRAS, NRAS, or MEK1., RSK regulates activated BRAF signalling to mTORC1 and promotes melanoma growth, Data show clinical significance to BRAF(L597) mutations in melanoma., In CRC patients treated with cetuximab, activating mutation signatures for BRAF (58 genes) were developed., Preoperative BRAF mutation was a predictive factor for occult contralateral papillary thyroid microcarcinoma presence., 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., we found no cases of Rosette-forming glioneuronal tumors of the fourth ventricle showing KIAA1549-BRAF gene fusion or BRAF (V600E) mutation, these results link epigenetic genes to methylation and suppression of tumor suppressor genes as a mechanism involved in BRAFV600E-promoted melanoma tumorigenesis and uncover a novel molecular signature that predicts a poor prognosis of melanoma., No BRAF V600E mutations were detected in nonserous epithelial ovarian tumors., Single Nucleotide Polymorphisms in BRAF gene is associated with diseases., 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., RAF1(D486N), as well as other kinase-impaired RAF1 mutants, showed increased heterodimerization with Braf, which was necessary and sufficient to promote increased MEK/ERK activation., Investigated BRAF and RAF1 alterations in Chinese prostate cancer.Found BRAF truncated in five of 200 informative Chinese cases & RAF1 was truncated in three of 204 informative cases and genomic rearrangements were correlated w/high Gleason scores., This study reveals a novel mechanism of immune suppression sensitive to BRAF(V600E) inhibition, and indicates that clinical blockade of IL-1 may benefit patients, A review summarizes the role of the BRAF V600E mutation in the development and progression of thyroid cancer., BRAFV600E mutation is associated with Langerhans cell histiocytosis., The BRAFV600E occurs exclusively in papillary thyroid carcinoma and papillary carcinoma-derived anaplastic cancer, rising as a specific diagnostic marker for this tumor when identified in cytological / histological exams, High-throughput genotyping in metastatic esophageal squamous cell carcinoma identifies phosphoinositide-3-kinase and BRAF mutations., Cardio-facio-cutaneous syndrome is caused by heterogeneous mutations in BRAF gene., High prevalence of BRAF V600E mutations is associated with Erdheim-Chester disease but not in other non-Langerhans cell histiocytoses., This study reveals a novel molecular mechanism underlying the regulation of feedback loops between the MAPK and AKT pathways., A K601E BRAF mutation is associated with papillary thyroid carcinoma., The results of this study supported an important role for BRAF duplication and MAPK pathway activation in gliomas of the optic nerve proper., MSI status, KRAS and BRAF mutation rates varied remarkably among the colonic carcinoma subsites irrespective of right- and left-sided origin., The presence of a BRAF c.1799T>A (p.V600E) mutation is associated with significantly poorer prognosis after colorectal cancer diagnosis among subgroups of patients., 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%., BRAF(V600E) mutation is an early event in thyroid carcinogenesis, and is associated with distinctive morphology and aggressive features even in papillary thyroid microcarcinomas, ARAF seems to stabilize BRAF, BRAF mutation is associated with early stage disease and improved outcome in patients with low-grade serous ovarian cancer., 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., Thus, in this meta-analysis, the BRAF mutation in PTC was significantly associated with PTC recurrence, lymph node metastasis, extrathyroidal extension, and advanced stage AJCC III/IV., Data indicate that KRAS, BRAF, PIK3CA, and AKT1 mutations can be rapidly and accurately detected for cancer diagnosis., The BRAF V600E mutation is the only independent predictor of compartment lymph node metastasis in papillary thyroid carcinoma., 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)., Higher response rates and longer time to progression were observed with selumetinib-containing regimens in patients who had melanoma that harbored a BRAF mutation., found a significantly increased risk of papillary thyroid carcinoma attributed to the SNP variants rs17161747, rs1042179, and rs3748093 for those with a family history of cancer, for smokers, and for both those of age <45 years and nondrinkers, This report is the first to identify the rare, variant BRAF V600D mutation in LCH, and provides support for constitutively activated BRAF oncogene-induced cell senescence as a mechanism of regression in congenital, benign LCH., consistent with previous studies, it was concluded that the incidence of BRAF V600E mutation in adult acute lymphoblastic leukemia, if any, is extremely infrequent, B-RAF upregulates SGLT1 activity, an effect requiring vesicle insertion into the cell membrane., BRAF mutation is suggested to be poor prognostic factors in CRLM., Braf mutation status is not significantly associated with poor survival for melanoma in Koreans., EGFR and downstream genetic alterations in KRAS/BRAF and PI3K/AKT pathways have roles in colorectal cancer and treatment [review], Immunohistochemistry is highly sensitive and specific for the detection of V600E BRAF mutation in melanoma., 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., We describe 3 patients with BRAF V600E mutation metastatic melanoma in whom treatment with vemurafenib resulted in prompt extracranial disease response but progression of metastatic disease in the brain., Studied the cytotoxicity and anti-tumour activity of novel MEK inhibitor, E6201, in a panel of melanoma cell lines. Most melanoma cell lines were sensitive or hypersensitive to E6201; the sensitivity correlated with wildtype PTEN and mutant BRAF status., Findings support the potential use of immunohistochemistry as an ancillary screening tool to assess the BRAFV600E mutation status in primary cutaneous melanoma., Increased BRAF mutation with age along with the lack of a UVR magnitude-BRAF mutation association suggests that duration of exposure rather than UVR exposure dose is the more likely link to acquiring mutations in melanocytic nevi., KRAS and BRAF mutations are infrequent or absent, respectively in Intestinal-type sinonasal adenocarcinoma, BRAF mutation was associated with lymph node metastases (LNM), advanced stage, extrathyroidal extension, tumor size, male gender, multifocality, absence of capsule, classic PTC, and tall-cell variant papillary thyroid cancer., A systematic review and meta-analysis revealed that BRAF mutation is an absolute risk factor for patient survival in colorectal cancer and melanoma., BRAF mutation was not found to be significantly associated with lymph node metastasis in patients with papillary thyroid cancer, The BRAF(V600E) mutation was demonstrated to be a poor prognostic factor for the persistence of the disease independent from other clinical-pathological features in low-risk intrathyroid papillary thyroid carcinoma patients., Histopathologic changes suggesting prolapsed rectal mucosa should take precedence over BRAF results in diagnosing sessile serrated adenomas in the rectum., analysis suggests that BRAF mutations occur at a low frequency in chronic lymphocytic leukemia, Desmoplastic malignant melanoma, BRAF mutation is associated with pleomorphic xanthoastrocytomas with anaplastic features., 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., 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., Study demonstrates that chromosomal instability commonly occurs in advanced BRAF mutant/MSS colorectal cancers where it may contribute to poorer survival, and further highlights molecular similarities occurring between these and BRAF wild type cancers., One hundred and ten patients (51%) were identified who were potentially nonresponders to anti-EGFR therapy, BRAFV600E mutation is associated with cervical lymph node metastasis and recurrence in papillary thyroid cancer., Clinical characteristics of colorectal cancer with the V600E BRAF mutation., These findings indicate that ABCG2 confers resistance to vemurafenib in A375 cells, suggesting involvement of this transporter in acquired resistance to vemurafenib., Data indicate that the presence of the BRAF V600E mutation was more frequent in women, but this gender difference was not statistically significant., In Chinese colorectal carcinoma patients, BRAF mutation is associated with 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., BRAF mutational status is predictive of papillary thyroid carcinoma recurrence, V600E point mutation was identified in the BRAF gene in 3 intramucosal nevi and in 2 melanomas. Only 1 blue nevus harbored the GNAQ209 mutation, BRAF mutation as a new serum marker for papillary thyroid carcinomas were not detectable in patientts diagnosed with thyroid neoplasms., data confirm that among lymphoproliferative disorders, BRAF V600E mutation is restricted to hairy cell leukemia (HCL); no mutations were identified in variant HCL, NMZL, ENMZL, PTLD, PTCL, ALCL, or LGL proliferations, The BRAF(V600E) mutation might be associated with a more aggressive phenotype and a poor prognosis in classic variant of papillary thyroid carcinomas., BRAF (V600E) mutation is associated with papillary thyroid carcinomas., BRAF mutations were correlated with poor overall survival in the full patient cohort, 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, Oncogenic B-RAF(V600E) signaling induces the T-Box3 transcriptional repressor to repress E-cadherin and enhance melanoma cell invasion., Aim of this work is to provide a detailed comparison of clinical-pathologic features between well-differentiated and poorly differentiated tumors according to their BRAF and RASSF1A status., BRAF (V600E) mutation is associated with papillary thyroid microcarcinoma., BRAF (V600E) is non-associated with Gal-3 expression, whereas it is associated with cytoplasmatic localization of p27kip1 and higher CK19 expression in papillary thyroid carcinoma., 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., results suggest that mutant B-RAF signaling downregulates Tiam1/Rac activity resulting in an increase in N-cadherin levels and a decrease in E-cadherin levels and ultimately enhanced invasion, Mutations affecting BRAF, EGFR, PIK3CA, and KRAS are not associated with sporadic vestibular schwannomas., the BRAF V600E mutation is not pathobiologically relevant in primary central nervous system lymphoma, Patients with V600R BRAF mutations can be treated successfully with oral BRAF inhibitors., Data indicate that BRAF and EGF receptor or SRC family kinase inhibition blocked proliferation and invasion of the resistant tumors., the role of BRAF mutations in melanoma and colorectal cancer, focusing on similarities and differences of BRAF mutations (Review), The status of BRAF(V600E) mutation was more frequent in multifocal PTC patients with lymph node metastasis and diagnosis at later age., we deduce that in the absence of mutation activation, B-Raf overexpression or downregulation is a protective event, since it delays the development of both malignant and benign thyroid tumors., BRAF mutation is associated with esophageal squamous cell carcinoma., Preoperative mutation screening for BRAF(V600E) does not meaningfully improve risk stratification and is unlikely to alter the initial management of patients with indeterminate nodules., Pulmonary Langerhans cell histiocytosis appears to be a clonal proliferation that may or may not have BRAF V600E mutations., Studies indicate that BRAF mutations are identified in 40-50% of patients with melanoma, and treatment with either of two BRAF inhibitors (vemurafenib, dabrafenib) or the MEK inhibitor trametinib is associated with improved clinical benefit., No point mutations were identified in BRAF codon Val600Glu in the studied colorectal adenocarcinomas in the Turkish population., High BRAF is associated with metastatic melanoma., This study shows that BRAF mutation occurs in Nigerian colorectal cancers., Results demonstrated the action of Dabrafenib and the inhibition of MAPK pathway in melanoma cell lines carrying BRAFV600D/R mutations; these results could be helpful to enlarge the number of patients who may benefit of a more effective targeted treatment, BRAF mutations is associated with colorectal cancer., Human neural crest progenitor cells are susceptible to BRAF(V600E)-induced transformation., no association with BRAF-V600E mutation in gastroeosophageal tumors, Data indicate that besides confirming the constant presence of BRAF-V600E in all patients with hairy cell leukemia, phospho-ERK1/ERK2 expression was observed., Ras pathway activation via EGF treatment induced strong binding between B-Raf and C-Raf and a low level of binding between B-Raf and A-Raf., Alternative splicing of exons 14, 15, 15b, 16b and 16c occurs in a considerable fraction of BRAF mRNA in normal colon and colorectal cancer cells and is independent of the V600E mutational status of the parental allele., The detected Merkel cell polyomavirus prevalence in non-small cell lung cancer in combination with the deregulated expression of BRAF and Bcl-2 genes suggests that these events are likely to contribute to the pathogenesis of non-small cell lung cancer., Kidins220 is a novel T-cell receptor (TCR)-interacting protein that couples B-Raf to the TCR. Kidins220 is mandatory for sustained Erk signaling and is crucial for TCR-mediated T cell activation., This is the first report of BRAF V600E mutation in endometrial cancer, indicating that it may contribute to tumorigenesis of endometrial cancer, although at a low frequency compared with KRAS mutations., study suggests that highly aggressive papillary thyroid microcarcinoma may arise in a subset of patients with BRAF(V600E) mutation and tumors greater than 5 mm; multivariate analysis showed that tumor recurrence was not associated with BRAF(V600E)mutation, BRAF and codon 12 KRAS mutations predict for adverse outcome of colorectal cancer patients receiving cetuximab., Report BRAF mutations in ovarian serous carcinoma., The role of BRAF V600E as targetable driver mutation in lung adenocarcinoma is strengthened by finding that in vivo expression of V600E in mice leads to development of invasive adenocarcinoma, a phenotype that is reversed when V600E expression is stopped., Studies identified 21 deleterious mutations MLH1, MSH2, MSH6 and BRAF., The BRAF gene polymorphism (rs10487888) may not be a genetic determinant for increasing the risk of chronic periodontitis among the Iranian population, AURKB and WEE1 are targets and biomarkers of therapeutic efficacy, lying downstream of (V600E)B-RAF in melanomas., study identified two miRNAs (miR-21* and miR-203 that are differentially expressed in papillary thyroid carcinoma tissues with BRAF(V600E) and revealed their associations with clinicopathological features, BRAF(V600E) increases migration and invasion of thyroid cancer cells via upregulation of Snail with a concomitant decrease of its target E-cadherin., BRAF V600E mutation was detected in 41/71 (58 %) gangliogliomas by immunohistochemistry, DNA sequencing was concordant in 60 of 62 analyzed cases, and BRAF V600E-mutated protein was localized predominantly to the neuronal compartment., This study demonistrated that Dysembryoplastic neuroepithelial tumors share with pleomorphic xanthoastrocytomas and gangliogliomas BRAF(V600E) mutation and expression., Data indicate that tumor regression was seen in three of five patients with BRAF-mutated, low pAKT melanomas., MITF-BCL2A1 as a lineage-specific oncogenic pathway in melanoma and underscore its role for improved response to BRAF-directed therapy., An analysis of BRAF mutations in fast-growing melanomas., The Mcl-1 promoter is dependent on a STAT consensus-site for B-RAF-mediated activation., In this manuscript, we provide an overview of the emerging scientific literature on dermatological adverse events arising out of BRAF inhibition., V600R mutation and double (V600E -V600M) mutation were identified in two melanomas, BRAF V600E mutation testing modifies sensitivity or specificity of the Afirma Gene Expression Classifier in cytologically indeterminate thyroid nodules., Melanomas with activation of the BRAF/MAPK pathway have suppressed levels of MITF and PGC1alpha and decreased oxidative metabolism, BRAF mutation shows clinical significance in the prognosis of thyroid papillary cancer., Results document the expression of RAC1b in normal thyroid cells as well as overexpression in a subset of PTCs. They suggest a possible interplay between BRAF V600E and RAC1b contributing to poor clinical outcome., The novel melanoma cell lines were compared to metastatic cell lines (HBL, LND1), wild type (wt) for MC1R and BRAF genes., This study confirms that the BRAF mutation is differentially detected in each variant of papillary thyroid cancer and is strongly correlated with unfavorable clinicopathologic factors., follow-up BRAFV600E mutation analysis may be helpful in the diagnosis of selected thyroid nodules negative for BRAFV600E mutation on initial analysis, which are assessed as suspicious malignant on ultrasonography., A BRAF mutation was only detected in a single Japanese gastric cancer., Aberrant BRAF splice variants with deletions in both kinase and RAS-binding domains in rheumatoid arthritis patients demonstrate that these BRAF splice variants constitutively activate MAPK through CRAF, genetic association studies in population in Italy, in cells expressing KIAA1549-BRAF, the fusion kinase functions as a homodimer that is resistant to PLX4720 and accordingly is associated with CRAF-independent paradoxical activation of MAPK signaling, Molecular analysis of the BRAF T1799A mutation in fine needle aspiration biopsy specimens has high specificity and positive predictive value for papillary thyroid carcinoma, In human BRAF papillary thyroid carcinomas, ERK kinase phosphorylation is decreased compared to normal thyroid glands., BRAF V600E mutation may identify a subset of grade 2 diffuse gliomas that have a distinct phenotype, incl. supratentorial location, chronic seizure disorder, and atypical radiographic and histologic features., 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., Data indicate that concurrent BRAF and PI3K/mTOR blockade results in induction of apoptosis., A high percentage of epithelioid giant cell glioblastoma multiformemanifest BRAF V600E mutation, Antitumor effects of vemurafenib are mediated by inhibiting oncogenic MAPK signaling in BRAF(V600)-mutant metastatic melanoma. Data suggest that inhibition downstream of BRAF should help to overcome acquired resistance., In this retrospective multicenter study, the presence of the BRAF V600E mutation was significantly associated with increased cancer-related mortality among patients with papillary thyroid carcinom, Accurate diagnosis of rare BRAF mutations is crucial. Pyrosequencing is accurate, highly sensitive, reliable, and time saving to detect rare BRAF mutations., The overall BRAF V600E mutation rate was 70.4% and 100% in tall cell variant., and SSCA followed by Sanger sequencing are effective two-step strategies for the detection of BRAF mutations in the clinical setting., Our findings confirm that BRAF mutations originate in the serrated epithelium of colonic perineuriomas with crypt serration, the clinical pathological relevance of BRAF mutation in cancer (Review), A combination of solid nodules, nodules with irregular contours, symptomatic nodules, and positive BRAF mutation has high predictive value for malignancy in patients with thyroid follicular lesion of undetermined signifi-cance., We show that (V600E)BRAF upholds the activity of glycolysis and therefore the addiction to glycolysis de facto becomes an addiction to (V600E)BRAF., BRAF alterations are associated with pediatric low grade gliomas and mixed neuronal-glial tumors., 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., BRAF mutation is associated with poor response to anti-EGFR MoAbs and it is an adverse prognostic biomarker of the survival of patients with metastatic colorectal cancer., 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., 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, Braf mutations were not associated with the risk of lymph node metastasis in papillary thyroid carcinoma., Detection of the BRAF V600E mutation in colorectal cancer by immunohistochemistry is a viable alternative to molecular methods, A BRAF mutation-specific (V600E) antibody detected tumors with BRAFV600E mutations and exhibited complete concordance with a DNA-based method., Establishment of molecular subgroups based on KRAS and BRAF mutation status is important and should be considered in future prognostic studies in colorectal carcinoma., low BRAF as well as NRAS expression levels were associated with a longer progression-free survival in the total population, BRAFV600E mutation is not associated with papillary thyroid carcinoma., We found BRAF(V600E) mutations in the melanocytic nevi to be fully clonal, strongly suggesting that BRAF-activating mutations typically are early initiating events in melanocytic neoplasia., Case Report, BRAF mutations are associated with papillary thyroid carcinoma., report that Mps1/AKT and B-Raf(WT)/ERK signaling form an auto-regulatory negative feedback loop in melanoma cells, Selumetinib plus dacarbazine showed clinical activity in patients with BRAF-mutant cutaneous or unknown primary melanoma, reflected by a significant benefit in progression-free survival., The mutations of EGFR and BRAF genes were not found in HER2-mutated patients with brain metastasis from non-small cell lung cancer., BRAF mutation in the elderly is also exclusive of papillary carcinoma and is often significant. Furthermore, it is related to the classic variant and possibly to thyroid extravasation, Both the CRP single nucleotide polymorphism rs7553007 and KRAS/BRAF mutations were independent prognostic factors for colorectal cancer patients with synchronous liver metastasis., Although moderate or strong cytoplasmic staining is specific for BRAF V600E mutations in colorectal adenocarcinoma, the VE1 monoclonal antibody is insufficiently sensitive to serve as an effective screening tool., We found that inherited variants of CDKN2A have no effect on the prevalence of BRAF/NRAS mutations in melanoma., BRAF mutations are associated with colorectal neoplasms., demonstrating that the BRAF(T1799A) mutation is a clonal event in thyroid cancer, The results indicate that BRAF mutant is a predictive biomarker for poor prognosis in mCRC patients undergoing anti-EGFR MoAbs therapy, especially in KRAS WT patients, BRAF, NRAS, and c-Kit molecular analyses among patients affected by nail apparatus melanoma were investigated., BRAF mutation rates varied by geographic location but not based on UV radiation, Sinonasal intestinal-type adenocarcinomas share common alterations of the EGFR pathway with colorectal adenocarcinomas, except for a lower frequency of KRAS and BRAF mutations., 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., The findings support the hypothesis that BRAF-mutated cells may show resistance to the anticancer effects of aspirin in patients with colorectal cancer., evaluated the survival impact of MET expression in patients with BRAF(V600E/K) advanced melanoma treated with vemurafenib, The present study demonstrates that concomitant BRAF mutation and RET/PTC rearrangement is a frequent event in papillary thyroid carcinoma., an unexpectedly higher frequency of BRAF mutations was observed in mucosal melanomas in Southern Italy., BRAF mutations are associated with lung cancer., This study investigated the impact of KRAS, NRAS, BRAF, PI3KCA and TP53 status on outcome of elderly metastatic colorectal cancer patients, BRAF V600E mutated tumour cells was detected in the cortical tumour component, pronounced leptomeningeal tumoural stroma was predominantly negative for VE1 binding. BRAF V600E mutation affects a subset of desmoplastic infantile astrocytoma/ganglioglioma., Although no melanomas had high-level amplification of BRAF, the two patients with progressive disease as their best response had BRAF copy gain in their tumors, 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, BRAF mutations are found in 2 to 4% of non-small cell lung cancers. The mutations harbor non-V600E mutations in 40 to 50% of cases. A phase 2 trial of dabrafenib described 8 responses of 20 patients with BRAF V600E mutant NSCLC, Although BRAF mutation appears to play a role in local tumour progression, it is not a risk factor for poor prognosis or tumour recurrence in papillary thyroid carcinoma, demonstrate dose-dependent effects of oncogenic signaling, with physiologic Braf(V600E) expression being sufficient for hyperplasia induction, 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%., Patient-derived tumor xenografts provides 'real-time' results in an animal that phenocopies the biology and expected vemurafenib responses of the tumor in a patient with BRAF V600E melanoma., The study found a high concordance of BRAF 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., No evidence existed for a differential prognostic role of BRAF mutation by MSI status (P(interaction) > .50). Combined BRAF/MSI status in colorectal cancer is a tumor molecular biomarker for prognosic risk stratification., BRAF V600E mutations occurs infrequently in endometrial cancer., Shifted termination assay fragment analysis can detect BRAF V600 mutations in formalin-fixed paraffin-embedded papillary thyroid carcinoma samples., Classification of serrated lesions using immunohistochemical evaluation of BRAF V600E mutation may identify lesions with higher potential to progression into sessile serrated adenoma/polyp, and further to BRAF V600E-mutated colorectal cancer., TIMP-1 protein expression is a reliable surrogate marker for BRAF(V600E)-mutated status in papillary thyroid carcinoma, Ras-mutant cancer cells display B-Raf binding to Ras that activates extracellular signal-regulated kinase and is inhibited by protein kinase A phosphorylation, Suppression of TORC1 activity in response to RAF or MEK inhibitors, as measured by decreased phosphorylation of ribosomal protein S6 (P-S6), effectively predicted induction of cell death by the inhibitor in BRAF-mutant melanoma cell lines., In our Near Eastern cohort, the BRAF mutation rate varied significantly by geographic location. In patients with multiple dysplastic nevi examined, discordant BRAF mutation status potentially negates an underlying constitutional predilection, Our studies have identified a previously unrecognized regulatory role of Lys63-linked polyubiquitination in BRAF-mediated normal and oncogenic signalings., Findings support the development of CDK and Raf co-targeting strategies in EGFR/HER-2-overexpressing or RAS/RAF mutant breast cancer (BC)., These findings demonstrate the presence of mutation-specific clinical differences between different BRAF genotypes in patients with melanoma, and support the incorporation of this information in patient evaluation and clinical trial design., The frequencies of EGFR, KRAS, BRAF, and HER-2 mutations in BM-NSCLC were 2.6, 38.5, 0, and 0% respectively., used a mutation-specific antibody for immunohistochemical detection of the BRAF V600E mutation and correlated expression with clinicopathologic features in papillary thyroid carcinoma, Report relatively high frequency of BRAF(V600E) and KIT mutations in amelanotic melanoma., BRAF V600E-mutated protein may be valuable in the diagnostic evaluation of these glioneuronal lesions and the observed association with mTOR activation may aid in the development of targeted treatment involving specific pathogenic pathways, Mortalin mediates a switch in tumor-suppressive signaling of Raf/MEK/extracellular signal-regulated kinase., BRAF mutation is associated with the serrated morphology of traditional serrated adenoma, detection of BRAF V600E in colorectal cancer specimens by immunohistochemistry is sensitive and specific and may help to identify Lynch syndrome patients, This study demonstrated the absence of consistent recurrent chromosomal alterations in desmoplastic infantile astrocytomas and desmoplastic infantile gangliogliomas and overall rarity of the BRAF mutation in these tumors., the association between BRAF V600E mutation and aggressive features of papillary thyroid cancer, BRAF mutations were detected in 2 amelanotic acral melanoma cases, BRAF(V600E) mutation is predictive for distant metastasis in papillary thyroid carcinoma but not positively., 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 occurs at similar frequencies as NRAS in acral lentiginous melanoma of Swedish patients, Significant difference in Progression-free survival (PFS) and overall survival (OS)between patients with BRAF mutated and BRAF wild-type tumours was not detected, 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., BRAF mutations were associated with reduced overall survival among patients with cololectal cancer without KRAS mutations in exon 2 and among those with NRAS mutations in exon 3., We found BRAF mutations in 13/61 of the melanoma lesions and V600K predominated over V600E., There was no significant association between BRAF positivity and tumor multicentricity, lymphovascular invasion, extranodal extension, central neck involvement, advanced stage (stage III or IV), and distant metastasis., BRAF protein mutation can be reliably detected in patients diagnosed with papillary thyroid carcinoma., The BRAF mutation was positive in 37 % of papillary thyroid carcinoma patients. It had no prognostic impact. Cause-specific survival of mutation-positive high-risk patients was poorer than CSS of mutation-negative high-risk patients., High rate of BRAF-KIAA1549 fusion is associated with pilocytic astrocytoma., The BRAF mutation represents an additional risk factor only in some subpopulations of colorectal cancers, in others having limited prognostic value., hypothesize that the level of SPRY2 expression contributes to MAPK/ERK pathway output and accounts for BRAF V600E+ and clinical heterogeneity in papillary thyroid cancer, Data indicate that phosphorylation of BRAF by AMPK disrupts its association with KSR1., The low incidence of BRAF mutation limited assessment of its prognostic impact., BRAF mutation appears to be associated with distinct, unfavourable clinicopathological characteristics in colorectal cancer - systematic review and meta-analysis, The kinase activity of BRAFV600E/L505H was higher than that of BRAFV600E, resulting in cross-resistance to a MEK inhibitor, EGF, which signals through CRAF, and an activated BRAF mutant also activate PKC and stimulate cell migration through up-regulating RFFL expression., BRAF mutational analysis was performed on tissue from 104 patients, BRAF signalling increases Mcl-1 expression in cutaneous metastatic melanoma, No mutations were found in the BRAF gene in a cohort of 84 patients affected by squamous cell anal cancer, HSP60 protein expression may inhibit lymph node metastasis in papillary thyroid carcinomas harboring the BRAF mutation., evaluated the potential role of XIAP expression as a novel prognostic marker to predict recurrence, in combination with the BRAF(V600E) mutational status in papillary thyroid cancer, 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., results provide evidence that constitutively activated BRAF(V600E) drives aberrant proliferation of monocyte-lineage cells., B-Raf mutations are associated with cancer., Based on this methodology and other published results for the BRAF mutation, we believe that it is now feasible and cost effective for the UK NHS to BRAF co-test all Thy4/Bethesda Class V thyroid FNAs., Results sugggest that Cdx2 may play a role in the serrated pathway to colorectal cancer with BRAF(V600E), CpG Island Methylator Phenotype (CIMP)-high and mismatch repair (MMR)-deficiency., When supplemented with other noninvasive test methods, the B-RAF(V600E) test could be a powerful adjunct with extensive clinical applications for diagnosis of thyroid nodules. (review), study characterized the multiple-dose pharmacokinetics of vemurafenib 240-960 mg twice daily (bid) in BRAF(V600E) mutation-positive metastatic melanoma patients, using the commercial formulation, Data indicate that the median time to progression (TTP) 8.9 months is close to the promising BRAF- and MEKi combination therapy with median progression-free survival (PFS) 9.4 months., As heterogeneity with respect to BRAF mutation status is detected in melanoma patients, subsequent testing of initially wild-type patients can yield different results and thus make BRAF inhibitor therapy accessible., BRAF(V600E) mutation is not associated with papillary thyroid microcarcinoma., The study found a BRAF(V600E) mutation frequency of 54% (seven of 13) in brainstem gangliogliomas., Rapidly metastasizing malignant melanoma characterized by a rare BRAF mutation not responding to vemurafenib, associations were identified between miR-31, BRAF and prognosis in CRC, BRAF p.V600E colon tumors showed significant MEIS1 promoter methylation, which was associated with decreased MEIS1 gene expression., BRAF mutation in papillary thyroid carcinoma determined by IHC is associated with significantly increased risk of lymph node recurrence., Frequency of somatic BRAF mutations in melanocytic lesions from patients in a CDK4 melanoma family., B-RAF increases the cell surface protein abundance and activity of the type II Na+-coupled phosphate transporters NaPi-IIa and NaPi-IIb., A novel AKT1 mutant amplifies an adaptive melanoma response to BRAF inhibition., Detection of BRAF(V600E) in cytology specimens by pyrosequencing is a useful diagnostic adjunctive tool in the evaluation of thyroid nodules also in elderly subjects, genetic association study in population in Italy, The overall survival rate was not significantly different between patients with wild-type BRAF and those with V600E or non-V600E BRAF mutations in an Asian cohort., We conclude that a high proportion of PTC cases likely harbors the BRAF V600E mutation. This mutation can be used as an independent factor for predicting the recurrence and distal metastasis of PTC tumors., BRAF V600E mutation is a rare event in biliary tract cancer, accounting for only 1% of all subtypes, and is restricted to intrahepatic cholangiocarcinoma., BRAF-V600E mutation is associated with younger glioblastoma patients., These cases further expand the range of glial neoplasia in which epithelioid morphology is encountered, and add to the growing list of biphasic tumors harboring the BRAF V600E mutation, Provided there is adequate quantity of viable tumor cells, immunohistochemical testing any melanoma sample from a patient with metastatic disease will accurately determine BRAF status., This study demonstrated that temporal location, reticulin deposition and CD34 expression are associated with BRAF mutation in pleomorphic xanthoastrocytoma., BRAF fusions define a new molecular subset of melanoma, potentially comprising 4% to 8% of "pan-negative" cases., Molecular genetic tests revealed BRAF V600E mutation., there was no correlation between BRAF-positive primary focus of papillary microcarcinoma and more aggressive or recurrent disease, The KRAS mutation is not present in about one-third of CRC patients, and therefore other gene mutations need to be investigated to better understand the molecular mechanisms of CRC and its treatment., Braf(V600E)-driven tumors become addicted to autophagy as a means to preserve mitochondrial function and glutamine metabolism, The study identifies the BRAFV600E mutation as a significant molecular alteration in malignant peripheral nerve sheath tumors., BRAF V600E-mutation in metastatic colorectal cancer characterizes a subgroup of patients with distinct biologic, clinical and pathological features and is associated with very poor patients' prognosis., correlation between KRAS or BRAF mutations and prognosis was not observed, Report clinical consequences of high frequency of BRAF mutations in ameloblastoma., Response to vemurafenib suggests that BRAFV600 is an oncogenic driver in pediatric gliomas., study found CYP24A1 expression was increased in papillary thyroid carcinoma compared to benign multinodular goitre; expression was further increased in stage III and IV tumours; a strong correlation found between CYP24A1 overexpression and BRAF(V600E) mutation, meta-analysis suggested that extrathyroidal extension, lymph node metastasis, disease recurrence, and advanced TNM stage were associated with BRAF(V600E) mutation in papillary thyroid carcinoma, BRAF mutation decreases tumor response in first-line treatment whether cetuximab was given or not in patients with KRAS wild-type, and anti-EGFR MoAb produces a clear benefit in response rate in patients with BRAF and KRAS wild-type., 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, Data indicate that dual targeting of heat-shock proteins 90 (Hsp90) and BRAF(V600E) kinase provided combinatorial benefit in vemurafenib-sensitive melanoma cells in vitro and in vivo., Despite being an independent predictor of central node metastasis in small papillary thyroid carcinoma, BRAF did not add substantially to the overall prediction of occult central node metastasis., Report detection of BRAF mutations eligible for therapy with vemurafenib in melanoma patients., Targeted genotyping revealed BRAF p.Val600Glu in 95% of papillary craniopharyngiomas., BRAF mutational analysis by melt curve analysis is feasible in routine thyroid cytology, and in our series had a 100% specificity for PTC in subsequent histology. The application of BRAF analysis could be useful for indeterminate cytology, The B-RafV600E mutation detected in melanoma is not associated with a chronic exposure to the sun., Data reveal a mechanism by which BRAF(V600E) and PI3K signaling cooperate to regulate melanoma proliferation through AKT-independent effects on protein translation., Two V600E-negative hairy-cell leukemias had new pote mutations in exon 11 (F468C and D449E). Another HCL was BRAF wild-type in exons 2-17. All non-HCL lymphomas lacked BRAF mutations., The presence of BRAF mutations is positively associated with advanced tumor stage in African American colorectal cancer patients., Mutational events as well as over-expression of BRAF gene are highly implicated, independently, in the pathogenesis of thyroid cancer., A subset of patients with RAS(wt) CMML harbors BRAF kinase domain mutations that are potentially capable of activating the MAPK signaling pathway., Resistance mechanisms were identified in 58% progressing tumors and BRAF alterations were common. Gene expression analysis revealed that mitogen-activated protein kinase (MAPK) activity remained inhibited in 21% of resistant tumors., results probably indicate that BRAF mutation may not be the only key factor in melanoma tumorigenesis, and that there should be multiple alternative genetic pathways related to melanoma, Data show that a high proportion of cases of non-pulmonary Langerhans cell histiocytosis (LCH) and pulmonary LCH (PLCH) expressed the proto-oncogene protein B-raf (BRAF) V600E mutant protein., no significant survival differences were found according to BRAF-V600 tumor mutations in patients with primary melanoma., B-RAF is a powerful regulator of hERG channel activity and cell surface hERG protein abundance., Suggest that some patients with advanced melanoma who are BRAF-mutation positive may benefit from ipilimumab as the first part of their sequential treatment schedule., A novel mechanism for response was discovered whereby high expression level of CAV-1 at the plasma membrane disrupts the BRaf/CRaf heterodimer and thus inhibits the activation of MAPK pathway during dasatinib treatment., BRAF inhibition causes decreased CXCL8 secretion from melanoma cells and induce an immune response against the tumor associated with increased IFN-gamma, CCL4, and TNF-alpha., The finding of BRAF mutations in meningeal melanocytomas points to a potential initiating role of BRAF in transformation toward malignancy and could have therapeutic implications in these specific melanocytomas., we sought to analyze the nature of IC and EC response and progression in patients with melanoma brain metastases treated with dabrafenib, and hypothesized that metastases respond and progress similarly to BRAF inhibitors., B-cell receptor functions differ in hairy cell leukemia displying BRAF V(600)E and mutated IGHV., Two cases of classic HCL, 1 showing CD5 expression, were truly BRAF V600E-negative based on negative results by PCR and sequencing despite high-level leukemic involvement, For the 598 (91%) patients with BRAF(V600E) disease, median overall survival in the vemurafenib group was 13.3 months (95% CI 11.9-14.9) compared with 10.0 months (8.0-14.0) in the dacarbazine group (HR 0.75 [95% CI 0.60-0.93]; p=0.0085), Molecular genetic analysis revealed BRAF duplication and a KIAA1549-BRAF fusion gene in 82% of group II tumors, but in none of the group I tumors, and a BRAF, we identify KIAA1549-BRAF gene fusions in 45 % of 82 low-grade glioma samples, Our results demonstrated that the BRAF V600E mutation is a common event in melanomas, representing an important molecular target for novel therapeutic approaches in such tumors., BRAF mutation in FVPTC is associated with unfavourable clinicopathological characteristics and malignant features on ultrasonography and may be a potential prognostic factor as it is in classical PTC., Nonsmall cell lung cancer cells with BRAF-V600E, but not other BRAF mutations, initially are sensitive to BRAF-inhibitor treatment, but rapidly acquire resistance to BRAF inhibition., BRAF-mutation analysis should be part of the subtyping of non-squamous NSCLC., BRAF mutation was significantly associated with a larger tumor size, extrathyroidal invasion and lymph node metastasis in papillary thyroid cancer., Although the sensitive pyrosequencing method was used, no EGFR, KRAS or BRAF mutations could be found, Report safety of vemurafenib in diverse population of patients with BRAF(V600) mutated metastatic melanoma., BRAF-V600 mutations are not associated with response to chemotherapy in stage IV melanoma., analysis of BRAF mutation and DNA methylation markers on fine needle aspiration biopsy specimens may be a useful strategy to facilitate the diagnosis of malignant thyroid neoplasm, BRAF mutation is associated with atypia of undetermined significance and papillary carcinoma., Meta-analysis demonstrated that the BRAF V600E mutation was significantly correlated with adverse pathological features of colorectal cancer and distinct clinical characteristics., BRAF mutations are virtually absent in melanomas originating from the vulva or vagina, BRAF V600E mutations may be more prevalent than previously thought in pediatric patients with papillary thyroid carcinoma, but do not correlate with aggressive disease characteristics, Anti-apoptotic BCL-2 proteins govern cellular outcome following B-RAF(V600E) inhibition and can be targeted to reduce resistance., Serrated colorectal carcinoma as proposed to arise from serrated adenoma is characterized by mutation of BRAF., Most of the Korean patients with multifocal papillary thyroid carcinoma (PTC) had the BRAF(V600E) mutation in one or more tumor foci, and all BRAF(V600E)-positive multifocal PTC showed more aggressive features., Melanomas with associated naevi have a higher frequency of BRAF(V600E) mutations than melanomas unassociated with naevi., In this large cohort, we found TERT promoter mutations to be common, particularly in Follicular thyroid carcinoma and BRAF mutation-positive papillary thyroid carcinoma, and associated with aggressive clinicopathological characteristics., findings suggest that subcategorization of AUS by cytomorphology and BRAF V600E mutation status is important for predicting the risk of malignancy, We evaluated the BRAF V600E expression by immunohistochemistry in pulmonary and extrapulmonary Langerhans cell histiocytosis cases, V600E mutations in 8/15 bile duct adenomas, BRAF-V600E expression in tissue dendritic cells did not define specific clinical risk groups but was associated with increased risk of recurrence., Although it has limitations, the VE1 antibody represents a feasible first-line approach for evaluating BRAF mutation status and may be a valid tool in the selection of samples for molecular analysis, KRAS and BRAF genes were wild-type in all squamous cell anal carcinoma cases., BRAF mutant/microsatellite stable (MSS) (BRAFmut/MSS) cancers (n = 33) and BRAF mutant/microsatellite unstable (MSI) (BRAFmut/MSI) cancers (n = 30) were compared for presence of copy number aberrations (CNAs) indicative of chromosomal insatbility., Increased BRAF mutation is associated with colorectal cancer progression and poor response to therapy., Studies indicate that the role of proto-cncogene protein B-raf-MEK-ERK pathway in controlling cell fate as a primary target for deregulated activation in cancer., Mutations in BRAF predict resistance to anti-EGFR therapies., Data support a central role of BRAF V600E mutation in Erdheim-Chester disease and suggest oncogene-induced senescense as a link to both inflammation and oncogenic mutation in histiocytes playing a role in the disease., Disruption of mutated BRAF signaling modulates thyroid cancer phenotype., This analysis suggests that differences in disease course of PTC in children versus adults are not strongly dependent upon the presence of the BRAF(V600E) mutation., genetic association studies in a population in Iran, analysis of a possible association between AID expression and BRAF mutation in melanoma, the outcome of 68 patients with advanced colorectal cancer and RAS, BRAF and PI3KCA status according to ALK gene status, is reported., Near-genomewide RNAi screening for regulators of BRAF(V600E) -induced senescence identifies RASEF, a gene epigenetically silenced in melanoma., A combined inhibition strategy targeting BRAF together with multiple erbB family kinases is potentially beneficial for treating BRAF V600E mutant melanoma., mutations in BRAF and NRAS are not mutually exclusive because they were simultaneously present in the same tumor specimens, the homebrew dispensation sequence unambiguously identifies all known BRAF mutations in this region, whereas the kit-based dispensation sequence has one unresolvable degeneracy that could be solved with the addition of two injections, BRAF mutation is associated with melanoma., Study found BRAF V600E mutations in 81 percent of papillary craniopharyngioma sampled, decreasing the levels of CTR1 (Cu transporter 1), or mutations in MEK1 that disrupt Cu binding, decreased BRAF(V600E)-driven signalling and tumorigenesis in mice and human cell settings, the BRAF pathway may contribute to the pathogenesis or malignant transformation of histiocytic and dendritic cell neoplasms., BRAF(V600E) mutation demonstrated to be an adverse prognostic factor indicating aggressiveness of papillary thyroid carcinoma, analysis of pro-death autophagic processes responsible for sensitization of BRAF-V600E glioma cells toward UAI-201, Response to this therapy suggests that BRAF inhibitors can affect primary CNS lesions when a documented and targetable mutation is present., long-term treatment with BRAF inhibitors can affect the interaction between BRAF/MAPK and Wnt/beta-catenin signaling to affect patient outcomes, Case Report, AKTi combined with BRAFi-based therapy may benefit patients with tumors harboring BRAF mutations and particularly PTEN deletions or AKT mutations., BRAF-mutant mCRC is associated with worse clinical outcome. Patients with BRAF-mutant tumors develop peritoneal metastases, less frequently present with disease limited to the liver, and have shorter survival after metastasectomy., 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, discordant BRAF mutation status is rare when samples from individual PTCs are compared or when samples from individual PTCs and lymph node metastasis at thyroidectomy are compared but occurs more when primary and recurrent metastasis are compared, The percentage of mutant BRAF alleles in papillary thyroid carcinoma is significantly associated with tumor burden and extrathyroidal invasion., The presence of dermoscopic peppering and thicker Breslow index ulceration suggest a morphological consequence of immune behaviour in BRAF-mutated melanomas, colorectal cancers with a BRAF mutation have distinct molecular features and resulted in a poor prognosis in Korean patients with advanced colorectal cancer, We conclude that a V600E BRAF mutation may not be helpful in distinguishing sporadic from MTS-associated sebaceous neoplasms, Data demonstrate that the BRAF(V600E) cooperates with either PIK3CA(H1074R) or with silencing of the tumor-suppressor PTEN, to promote development of anaplastic thyroid carcinoma., This study indicated that mutations of KRAS, PIK3CA and NRAS were rare in advanced gastric cancer., BRAF V600E is heterogeneously distributed in some papillary thyroid carcinomas(PTCs). The large BRAF V600E neoplastic cell subpopulations found in mutated cases is consistent with the view that the BRAF V600E is acquired early during PTC development., BRAF(V600E) mutation is not a useful prognostic marker, though it does influence the short- and medium-term outcomes of classic papillary thyroid cancer, BRAF V600E mutation is associated with refractory hairy cell leukemia., BRAF V600E mutation positive pediatric posterior fossa gangliogliomas exhibit no unique imaging features, are associated with shorter progression-free survival, and carry promising treatment implications by BRAF inhibitors, analysis of RAS, RET/PTC, and BRAF mutations in advanced stage of papillary thyroid carcinoma, Characteristics and prognosis of colorectal cancer with NRAS mutations are different from those with KRAS or BRAF mutations., Case Report, The present work discusses the most recent and controversial evidence on the BRAF V600E relevance in development and progression of thyroid tumors. [Review], Although VE1 antibody can be useful in the screening of colon carcinomas for BRAF V600E-mutant proteins, molecular genetic confirmation is always necessary for mutation diagnosis., RAC1b overexpression constitutes a marker of poor prognosis in KRAS/BRAF WT mCRC patients treated with first-line FOLFOX/XELOX therapy., The BRAF mutation was significantly associated with persistence/recurrence and a potential predictor in patients with classical PTC >10 mm at a BRAF mutation prevalent area, BRAF mutation cannot be regarded as a reliable marker of node metastases in patients with PTC., Overexpression of BRAF(V600E) in normal thyroid epithelial (H tori) cells also reduced the effects of Dkk-1 on cell survival., report of a new IDH1 mutation associated with BRAF mutation in a very unusual glial tumor., BRAF mutation is asociated with ameloblastoma., The high-resolution melting method developed was shown to be a reliable method for BRAF mutation detection, 12% of KRAS negative colorectal cancer showed BRAF gene mutation. Considering that 42% of samples have a KRAS mutation, 54% of patients should not respond to therapies with monoclonal antibodies directed against epidermic growth factor (EGFR) pathway., BRAF mutation was not associated with negative prognostic indicators or adverse outcomes in PTC., Data indicate that BRAF protein overexpression was significantly associated with thyroid extracapsular extension (ECE) and lymph node metastasis (LNM) positive cases., BRAF mutation is associated with melanoma nodal metastases and an unknown primary site., Treatment of HCL patients with vemurafenib, an inhibitor of mutated BRAF, resulted in normalization of HSPC frequencies and increased myeloid and erythroid output from HSPCs, While frequency rates of BRAF mutations were quite identical across the different MPM lesions, a significant increase of cKIT (p<0.001) and CyclinD1 (p=0.002) amplification rates was observed between first and subsequent primary melanomas, Genetic targeting of BRAF Valine600Aspartate drug resistance mutation identifies dabrafenib as a selective agent against BRAF-resistant colorectal cancer cells., Our results indicate a cross-talk between Braf and p300 in melanoma and demonstrate the importance Braf and p300 expression in the diagnosis and prognosis of melanoma., Findings suggest a link between Langerhans cell histiocytosis and Erdheim-Chester disease involving the BRAF(V600E) mutation., suboptimal specificity and PPV limits the diagnostic utility of both antibodies to reliably detect BRAF p.V600E mutations in thyroid carcinoma, The B-Raf(V600E) inhibitor dabrafenib selectively inhibits RIP3 and alleviates acetaminophen-induced liver injury., BET inhibition with I-BET151 appears independent of the BRAF and NRAS mutational status of melanoma, BRAF was a significant parameter for predicting multifocality in follicular variant of papillary thyroid carcinoma., 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., BRAF and NRAS mutation status does not influence survival in metastatic melanoma., BRAF V600E immunohistochemistry is reliable for the evaluation of mutational status in colorectal carcinoma regardless of site or prior treatment history, and staining shows a high degree of intratumoral homogeneity., Using the PCR test with sense allele-specific primers, mutations in V600 were found in 33 of 51 Russian patients (64.7%) with cutaneous melanoma., Results show that BRAF-mutated patients were significantly younger at the time of primary melanoma and first diagnosis of metastasis than BRAF wild-type patients but BRAF mutation is not associated with a more aggressive illness., a novel role for B-Raf in the selective regulation of alpha4beta1 integrin-mediated adhesion., Although both, DTIC and TMZ act as alkylating agents through the same intermediate, NRAS and BRAF mutant cells responded differentially only to DTIC., The 5-year survival rate of colorectal cancer patients with BRAF mutations was significantly decreased., BRAF mutations are associated with response to chemotherapy in cancer., amuvatinib has proapoptotic activity against melanoma cell lines, with selectivity observed for those harboring oncogenic NRAS but not BRAF, Considering the diagnostic performance and low reproducibility of US, the combination of FNA with BRAFV600E is the most reliable and objective method for diagnosing thyroid malignancy., Although there was large variability between patients, FDG uptake decreased with higher daily doses in patients with BRAFV600 mutation-positive melanoma, BRAF(V600) mutation is associated with melanoma., MSI and the BRAF(V600E) mutation have a prognostic impact in colon cancer, Results suggest tha tthe pathological progression from Serrated adenoma through colon carcinoma required the successive events, BRAFV600E mutation in primary tumor might be a promising molecular marker to predict the status of 131I uptake in distal metastases., BRAF mutations in NSCLC were significantly associated with adenocarcinomas ., The absence of CXCR4 expression and BRAF mutation in cancers with a minor PD component underlined different pathogenic and metastatic processes in comparison with WDCs., Activating FGFR2-RAS-BRAF mutations play a critical role in the pathogenesis of most cases of ameloblastoma., Our results highlight the low incidence of BRAF mutations and CIMP in CRC from Saudi Arabia., SOX2 expression is partly regulated by BRAF signalling, and an increased SOX2 expression may promote CRC metastasis and mediate a poor patient prognosis, 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, document two rare cases of massively metastatic spinal cord GGs in adult patients who were negative for BRAF V600E mutations via multiple methods, Coexisting BRAF V600E and TERT C228T mutations form a novel genetic background that defines PTC with the worst clinicopathologic outcomes, providing unique prognostic and therapeutic implications., Data indicate mutation in the proto-oncogene protein B-raf (BRAF) gene at the time of hairy cell leukemia (HCL) diagnosis in two cases., No BRAF mutations were detected in the lesions of 18 cases, Common BRAF mutations are not present in systemic mastocytosis 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., This study demonstrates that IHC analysis is a very sensitive test for evaluation of BRAF mutations in metastatic malignant melanoma and may be useful as an initial screening test., BRAF(V600E) mutations in primary cutaneous melanomas were associated with residence in locations with medium and high UV indices in mid-life., BRAF mutations were found in 8.7% of colorectal cancer precursor lesions, mainly associated with serrated polyps and absent in adenomas. In CRC cases, 6.5% exhibited BRAF mutation., BRAF V600 mutations are associated with pathological features in Japanese melanoma patients, Enforced expression of RAC1 P29S in sensitive BRAF-mutant melanoma cell lines confers resistance manifested by increased viability., NRAS expression and increased MAPK activation drive vemurafenib resistance in V600E BRAF+ve melanoma., BRAF mutation in pilocytic astrocytoma is associated with a more diffuse growth pattern but does not confer a more aggressive clinical behavior, Data indicate that BRAF mutant status and number of positive lymph nodes as the only independent prognostic factors for recurrence-free (RFS) and disease-specific survival (DSS)., 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., ETV1 expression is a rare event in human melanoma and seems to be rather based on hyperactivation of MAPK signals, by BRAF (V600E) mutation, than on ETV1 gene amplification., Prevalence of BRAF mutations in CRC patients is not high but extremely correlated with MSI and risk categories as BG, whereas they are absent in LS patients., It is a major negative mediator of the extracellular signal-related kinase (ERK)/mitogen-activated protein kinase and a substrate of cdk5 in neurons., loss of stem cell identity upon induction of BRAF/MAPK activity may represent a novel fail-safe mechanism protecting intestinal tissue from oncogene activation, Next Generation Sequencing (NGS) assay revealed three genomic alterations, activating V600E BRAF mutation can be frequently demonstrated in pediatric Langerhans cell histiocytosis, The prevalence of rare BRAF mutations was 0.76% of all BRAF-positive thyroid cancers, and the rare mutations were associated with less aggressive pathologic features., Our data suggest that the poor prognosis of dMMR is driven by the BRAF(MT) status., Multiple potential therapeutic targets were identified in metastatic unknown primary and cutaneous melanomas that lacked BRAFV600 and NRAS mutations, The potential role of combined MMR and BRAF IHC as prognostic markers in CRC., combination of microsatellite instability and BRAF status serves as both a prognostic and predictive marker and may provide much-needed guidance during the planning of therapeutic strategies, X-ray crystallography reveals a regulatory role for BRAF in the MAPK pathway independent of its kinase activity but dependent on interaction with MEK., V600E BRAF mutation is associated with synchronous and metachronous thyroid cancer coexisting with Langerhans cell histiocytosis., BRAF(V600E) mutation is associated with papillary thyroid carcinoma., 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., PTEN loss was significantly associated with OS and time to MBM in patients with BRAF(V600) mutations., This study suggests that BRAF mutation-related specific transcripts associate with a poor phenotype in melanoma and provide a nest for further investigation., Methylation of MLH1 is strongly associated with BRAF mutations in sporadic colorectal cancer., Targeted therapy in BRAF mutated melanoma; treatment with BRAF inhibitors and in combination with MEK inhibitors. [Review], this study sheds light on the pathogenesis of Serous borderline tumor ovarian tumors by showing that BRAF mutation is associated with cellular senescence, 6 different BRAF missense mutations were found in 9 of 11 patients with cadiofaciocutaneous syndrome., 33% of Langerhans cell histiocytosis cases with wild-type BRAF and none with BRAFV600E harbored somatic mutations in MAP2K1 (6 in-frame deletions and 1 missense mutation) that induced extracellular signal-regulated kinase (ERK) phosphorylation in vitro., Results reveal a BRAF(V600E)-directed pathway that mediates silencing of MLH1 and, more generally, is responsible for CpG Island Methylator phenotype., A high discordant rate was found in Braf mutation statuses between primary and metastatic cutaneous melanoma lesions., dual HSP90/TRAP1 inhibitor HSP990 showed activity against the TRAP1 network and high cytostatic potential in BRAF-mutated colorectal carcinoma cells, Data suggest that proto-oncogene potein B-raf (BRAF) V600E mutations are present in rare cases of dendritic cell and histiocytic disorders, and their identifi cation off ers a potential therapeutic target for these neoplasms., 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., BRAF mutation status was obtained for 146/160 cases. Overall mutation rate was 24/88 (27.3%) in primary and 25/58 (43.1%) in metastatic melanoma. V600E was the predominant mutation in 21/24 (87.5%) of primary and 23/25 (92%) of metastatic melanomas., Overexpression of HO-1 in a subset of thyroid cancers is associated with tumour aggressiveness and BRAF V600E expression, BRAF V600E allele frequency is associated with papillary thyroid cancer progression., BRAF mutations occurred in 2.2% of advanced-stage lung adenocarcinomas, were most commonly V600E, and were associated with distinct clinicopathologic features in comparison with other genomic subtypes and with a high mutation rate in more than 1 gene., 710 melanomas included in the study were located in sun non-exposed regions of the skin; this category of tumors was characterized by the highest occurrence of BRAF mutations, B-RAF mutations were frequently detected in aberrant crypt foci., we detected 15 additional mutated melanoma samples and two additional BRAF V600E mutations in metastatic colorectal cancer samples by the LightMix assay compared to Sanger sequencing., we identify that analysis of plasma and urinary cfDNA provides a reliable method to detect the BRAF(V600E) mutation and monitor response to therapy in these disorders., Data indicate an independent prognostic value of BRAF V600E mutation for papillary thyroid cancer (PTC) recurrence in various clinicopathologic categories., Report BRAF mutation status in colorectal neoplasms and neuroendocrine differentiation in primary/metastatic colorectal neoplasms., The BRAF(V600E)mutation iss significantly associated with several poor clinicopathologic characteristics, but was not associated with sonographic features, regardless of thyroid tumor size., BRAF V600E mutations are frequent in dysembryoplastic neuroepithelial tumors and subependymal giant cell astrocytomas., this study supports the idea that additional NK cell-based immunotherapy (by checkpoint blockade or agonists or cytokines) may combine well with BRAF(V600E) inhibitor therapy to promote more durable responses in melanoma., 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, our study demonstrated the BRAF V600E mutation was an independent prognostic factor for colon cancer patients., our data indicate that preexisting MEK1(P124) mutations are associated with a reduced response to BRAF inhibitor therapy and identify a subset of patients with BRAF-mutant melanoma likely to benefit from combination therapies, PD-L1 expression in melanocytic lesions does not correlate with the BRAF V600E mutation., discordancy of BRAF mutation status is not an infrequent finding between primary and metastatic melanoma., BRAF V600E inhibited NIS expression by the upregulation of its promoter methylation. Specific regions of CpG islands of NIS promoter in BRAF V600E harboring papillary thyroid carcinoma were highly methylated compared with surrounding normal tissue., Results demonstrate that mutated BRAF is associated with melanomas that are more aggressive.They are also associated with absence of solar elastosis and tumor epitheloid cells, we describe three interesting cases of paediatric glial and glioneuronal tumours harbouring both BRAF V600E and H3F3A K27M mutations., Concluded that the presence of BRAF(V600E) mutation in papillary thyroid carcinoma could be preoperatively predictive of extrathyroidal invasion in a Chinese population., The frequency of the BRAF mutation in cPTCs with suspicious US features was higher than that of cPTCs with negative US features regardless of the BSRTC., there is a lower incidence of brain metastases in patients with BRAF-mutated tumors who took vemurafenib before the diagnosis of brain metastases, 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., BRAF V600E mutation is related to lack of response and worse survival in wild-type KRAS metastatic colorectal cancer patients treated with anti-EGFR MoAbs., Preanalytical workflow optimisation may reduce errors in down-stream sequencing in BRAF mutation detection., Proteomic profile and in silico analysis in metastatic melanoma with and without BRAF mutation, Together, this work provides formal proof of an allosteric link between the RAF dimer interface, the activation segment and the catalytic infrastructure., BRAF V600E mutation status did not correlate with any clinicopathological parameters, The determination of BRAF mutational status is recommended in any cystic sellar lesion and can in most cases be provided by VE1 immunohistochemistry even in specimens of low cellularity., The consistency of the BRAF gene mutation in peripheral blood and tissue is high., Lymph node specimens with low tumor cellularity due to numerous adjacent lymphocytes may pose a challenge to clinical detection of BRAF mutations of melanoma., We documented three novel mutations in the BRAF gene in cardio-facio-cutaneous syndrome patients and correlated clinical findings with causative mutations in the BRAF or MEK1/MEK2 genes, The BRAF(V600E) mutation was significantly associated with lymph node metastasis and poor prognosis in papillary thyroid carcinoma., truncated RAF1 and BRAF proteins, recently described as products of genomic rearrangements in gastric cancer and other malignancies, have the ability to render neoplastic cells resistant to RTK-targeted therapy, The combined BAP1-BRAFV600E+ immunoprofile appears to be a constant feature of BAP1 tumor syndrome-associated melanocytic lesions, did not find a negative prognostic impact of a positive BRAF V600E mutation status on survival in papillary thyroid cancer, BRAF V600E mutation affects patients with large/giant congenital melanocytic nevi, and with neurocutaneous melanocytosis, a novel finding., global miRNA expression profiles in fresh-frozen metastatic melanomas in relation to clinical outcome and BRAF mutation, were examined., The V600E BRAF mutation in a borderline serous tumour of the testis is genotypic evidence of similarity with its phenotypic ovarian counterpart., These observations led us to conclude that increased TSH signaling overcomes OIS and is essential for B-RafV600E-induced papillary thyroid carcinogenesis., BRAF V600 mutation is associated with melanoma., Missense mutations were identified in the BRAF and KRAS genes in cutaneous melanoma cell line., This is the first observation of a secondary BRAF mutation in a vemurafenib-resistant patient-derived melanoma sample, which confirms the potential importance of the BRAF L505H mutation in the development of therapy resistance., BRAFV600E intratumor and intrapatient heterogeneity in melanoma is diminutive, nevertheless, the identified exceptions will have important implications for the clinical management of this disease., 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., The association between a host response and lymphovascular invasion and microvessel density in primary cutaneous melanoma with a BRAF mutation suggests that they exhibit potential for strategizing immunotherapies, To detect whether the V600E mutation is present or absent in the BRAF gene in melanoma patients is an important component in the evaluation of the biological behavior of tumor cells and their performance of biologically significant functions., in different macroscopic subtypes of colorectal adenoma, BRAF mutation (V600E) was found in 2 of 36 lateral spreading tumors and 1 of 34 polypoid lesions; mutations in KRAS, BRAF or PIK3CA occurred in a mutually exclusive manner, Data suggest that Sema6A and Mical1 may represent new potential therapeutic targets in BRAFV600E melanoma., Report BRAF VE1 immunoreactivity patterns in epithelioid glioblastomas positive for BRAF V600E mutation., This is the largest study on the aggressive role of TERT promoter mutations in anaplastic thyroid cancer(ATC), demonstrating an association of TERT C228T with BRAF V600E, older patient age, and tumor distant metastasis in ATC., BRAF V600E mutation is associated with Anaplastic thyroid cancer., BRAFV600E-mutation-positive papillary thyroid microcarcinoma are more likely to manifest with aggressive clinicopathological characteristics., melanoma cell lines selected for resistance to BRAFi+MEKi, but not those to BRAFi alone, displayed robust drug addiction, providing a potentially exploitable therapeutic opportunity., Data support a role for BRAF V600E immunohistochemistry in diagnostically challenging cases of metanephric adenoma and expand the spectrum of BRAF exon 15 mutations in this uncommon but unique renal neoplasm., high-resolution melt and allele-specific PCR could detect as low as 1.25% KRAS- or BRAF-mutant alleles., In the management of thyroid nodules with benign cytology but positive BRAF(V600E) mutation, thyroidectomy should be considered in nodules which have 2 or more suspicious US features and are considered discordant on image-cytology correlation., BRAF overexpression could be an independent factor causing tumorigenesis in gliomas regardless of phospho-EGFR expression., 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, BRAF mutations are associated with response to chemotherapy in colorectal cancer., KRAS and BRAF mutations are associated with inferior survival, independent of MSI status, in Japanese patients with curatively resected colorectal carcinoma., Report predictive value of immunohistochemistry in detecting BRAF mutations in neoplasms., Case Report, These findings suggest that prenylation inhibition may be able to target melanoma cells with mutant NRAS or with mutant BRAF and PTEN., HPV presence was not associated with age, stage or grade of tumours, MSI or mutations in KRAS, TP53 or BRAF genes., Report low rates of BRAF mutations in Chinese colorectal carcinoma patients., BRAF mutations are associated with Metastatic Colorectal Cancer., analysis of BRAF mutation and CDKN2A deletions in childhood secondary high-grade glioma, Review/Meta-analysis, Aberrant expression of A-, B-, and C-RAF, and COT is frequent in PTC; increased expression of COT is correlated with recurrence of PTC., analysis of BRAF 3'UTR isoforms in melanoma, Mutated KRAS and mutated BRAF seem to be prognostic factors in patients with Colorectal cancer who undergo lung metastasectomy., BRAF mutations in Non-small cell lung cancer are more likely in Adenocarcinoma, and BRAF V600E mutations are more frequent in women and never smokers., Suggest that continuing vemurafenib treatment beyond progression may be beneficial in BRAF V600 mutated advanced melanoma patients, who prior to progression responded to vemurafenib., All four tumors that recurred were LN+, with infiltrative borders, and lacked the BRAF mutation., Mutated BRAF mutant protein was detected in 53% of the bile duct adenomas and in none of the cases of bile duct hamartomas, Trametinib alone caused upregulation of p-AKT in BRAF non-V600 mutated cells., Data show that licochalcone A (LicoA) suppresses solar UV-induced cyclooxygenase (COX-2) expression by acting as a potent inhibitor of enzymes PI3K, MEK1, and B-Raf., BRAF is minimally prognostic in papillary thyroid carcinoma. However, prevalence of the BRAF mutation is 70% in the general population, providing the opportunity for targeted therapy., These findings enhance our understanding of factors cooperating with BRAF inhibition that accelerate keratinocyte oncogenesis as well as broaden the knowledge base of multifactorial mediators of cancer in general., A pathogenic BRAF(V600E) mutation was identified in a patient with Erdheim-Chester disease., No BRAF V600E mutations were seen in this cohort of non-infiltrative, non-invasive follicular variant of papillary thyroid carcinoma, genetic association studies in populations in Ireland and Belgium, BRAF mutation is not associated response to chemotherapy in melanoma., Results suggest that the presence of a BRAF mutation does not necessarily 'drive' more rapid tumour growth but is associated with poorer MSS in patients with early-stage disease, These tumors showed a markedly better prognosis, with molecularly PXA-like tumors frequently harboring BRAF V600E mutations and 9p21 (CDKN2A) homozygous deletion., No association was established between BRAF V600E mutation and regional lymph node metastasis in papillary thyroid carcinoma in Chinese patients., Radiotherapy with concomitant BRAF inhibitor therapy is feasible with an acceptable increase in toxicity. Vemurafenib is a more potent radiosensitizer than dabrafenib., The study demonstrates the activating BRAF mutation (V600E), which is found in multiple human cancers, is a driver of canine invasive cell carcinoma of the bladder, and highlights a urine-based test for quick diagnosis., Among the 779 cases, 150 cases were positive for BRAF (V600E) staining, including 38 (of 611, 6%) CRCs, 102 (of 127, 80%) PTCs and 10 (of 41, 24%) malignant melanomas., By this integrated approach, we found that patients with BRAF V600E mutation responded very well to broad acting drugs and there was no relation to prognosis in early-stage myeloma, Pediatric oligodendrogliomas (pODGs) can harbor the KIAA1549-BRAF fusion with aberrant MAPK/ERK signaling, and there exists an option of targeting these pathways in such patients., oncogenic activation of BRAF allows tumor cells to co-opt an evolutionarily conserved MHC-I trafficking pathway as a strategy to facilitate immune evasion., Preoperative targeted therapy of advanced BRAF-mutant melanoma is feasible, well tolerated, induces brisk tumor responses, and facilitates correlative science., No mutations in the BRAF gene were identified in patients with gastric cancer., This work supports the fact that BRAF V600 mutation is not implicated in meningioma tumorigenesis, The most important implication of these findings is that we could begin to treat patients with the BRAF V600E and CDKN2A alteration differently when they are first diagnosed than those with a lower risk for secondary high-grade glioma, BRAF mutation in cutaneous malignant melanoma plays an important role in the development of skin cancer in Asians. population., BRAF V600E mutation is associated with differentiating Rathke's cleft cyst with squamous metaplasia from papillary craniopharyngioma., these results may not only indicate some future applications of inhibitors targeting B-Raf(v600e), but also benefit B-Raf(v600e) harboring cancer patients., findings suggest that the BRAF(V600E) mutation can be detected using a PNA clamp real-time PCR in the blood of PTC[ papillary thyroid carcinoma ] patients with lung metastasis, Study reports that mice engineered to overexpress either the full-length murine B-Raf pseudogene Braf-rs1 and its human ortholog, BRAFP1, elicit their oncogenic activity, at least in part, as competitive endogenous RNAs (ceRNAs) that elevate BRAF expression and MAPK activation in vitro and in vivo., BRAF mutations often affect a limited fraction of transformed metastatic colorectal cancer cells., The SMOF412E mutation was not detected in ameloblastoma. The BRAFV600E-activating mutation is a common event in ameloblastomas, occurring regardless of site or histological type. This mutation is also detected in odontogenic carcinomas., The BRAFT1799A mutation was found in 38 cases (42.7%)., BRAF V600E mutation might be associated with right-sided tumors and subsequently related unexplained iron-deficiency anaemia (IDA) at presentation, The increased activity of the V600E mutant is twofold, The presence of TC was significantly associated with TERT promoter and BRAF mutations. BRAF did not influence patient outcome., Multifunctional bioscaffolds for 3D culture of melanoma cells reveal increased MMP activity and migration with BRAF kinase inhibition., Tumor dissemination in colon cancer patients is less likely to occur with the BRAF mutation., BRAF V600E mutation is associated with glioblastoma., 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, Histopathological prognostic markers (Breslow thickness, mitotic index, ulceration, tumor infiltrating lymphocytes pattern) did not show any differences depending on BRAF V600E mutational status, A complex mechanism driven by mutation BRAF (V600E) on melanoma tumorigenesis., associate higher expression of the ligand-receptor axis of TFF2 and CXCR4 with BRAF V600E-mutant colon cancer (P = 3.0 x 10(-3) and 0.077, respectively for TCGA; P = 3.0 x 10(-8) and 5.1 x 10(-7) for CIT), This review will focus on the science and clinical findings related to targeted therapies that inhibit BRAF or MEK as well as the immunotherapies that block the CTLA-4 or PD-1 pathways, BRAF V600 mutation is associated with melanoma., BRAF-induced tumorigenesis is IKKalpha-dependent but NF-kappaB-independent, Following B-RAF expression, MIR31HG is located mainly in the cytoplasm., Report increased frequency of BRAF proto-oncogene hot spot mutation V600E in cohort of colorectal cancer patients from Ahvaz City, southwest Iran., RNA expression profiles were compared between conventional BRAFwild type and BRAFmutation papillary thyroid carcinomas., 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, The patient carrying a concomitant BRAF mutation in temporal gangliogliomas and focal cortical dysplasia fell into Engel Class II., BRAF V600E Mutation is associated with papillary thyroid carcinoma., BRAF V600E mutation can be used as a supplementary molecular marker to aid in the diagnosis of Hairy cell leukaemia, Data show that proto-oncogene protein B-raf (BRAF) inhibition reduces melanoma glucose uptake per cell, but that this change is no longer significant following normalization for cell volume changes, Somatic BRAF mutation was found in a patient with syringocystadenoma., BRAF V600E Mutation is associated with Melanoma., BRAF immunohistochemistry(IHC) was strongly concordant with BRAF mutation test and had high diagnostic accuracy in BRAF mutation analysis of Papillary thyroid carcinoma.[review; meta-analysis], KIT-mutated patients had a worse outcome than PDGFRA-mutated or triple-negative (KIT, PDGFRA, BRAF wild-type) cases, reviews the current knowledge on the use and implications of BRAF mutational status in colorectal tumors, in order to define its present role in the clinical practice, we identified a new SND1-BRAF fusion that appeared to be present in a subpopulation of tumor cells., BRAF V600E immunostaining is a helpful marker for pediatric metanephric adenoma, BRAF protein play a role in the mitochondrial fragmentation in melanoma patients., BRAFV600E expression in melanocytes induces Schwannian differentiation in vivo, Case Report, Our data lead us to hypothesize that TERT promoter and BRAF mutations cooperate in cutaneous melanoma, BRAF-V600E mutations occur predominantly in female smokers with adenocarcinomas., detection of BRAF V600E by immunohistochemistry is useful in the distinction of hairy cell leukemias from other splenic-based lymphomas, According to results, oral benign peripheral nerve sheath tumours have a low LOH rate, but P53 locus alteration is occasionally found. Additionally, BRAF V600E mutation is either not relevant to the molecular pathogenesis of this group of lesions of the oral cavity, or may occur at very low rates., BRAF protein immunohistochemistry on fine needle aspiration can be important in the diagnosis of papillary thyroid carcinoma, BRAFV600E expression is homogeneous in melanoma tumors., This study confirmed the high frequency of KIAA1549, TRAP1 is a downstream effector of BRAF cytoprotective pathway in mitochondria and TRAP1 targeting may represent a novel strategy to improve the activity of proapoptotic agents in BRAF-driven CRC cells., LOH and TP53 mutations detected in lip squamous cell carcinoma and actinic cheilitis may be associated with tumorigenesis, whereas BRAF mutation does not seem to significantly contribute to LSCC pathogenesis, BRAF, NRAS and KRAS gene mutations in plasma cell dyscrasias may have a role MEK-ERK pathway activation, Given the high prevalence of lung cancer and the availability of targeted therapy, Chinese lung ADC patients without EGFR and KRAS mutations are recommended for HER2 and BRAF mutations detection, especially for those never smokers, Presence of BRAF V600E associated with aggressive tumor features in Papillary thyroid carcinoma, including invasion, metastasis, advanced TNM stage at presentation, low response to radioiodine treatment, recurrence, and tumor-related mortality., Report BRAF mutations and PD-L1 expression in disseminated histiocytoses., BRAF mutations were associated with central nervous system tumors., The BRAF mutation is a possible indicator for determining the extent of thyroidectomy required but not for the extent of lymph node dissection and prognosis in patients with conventional papillary thyroid carcinoma., Tissue micro array availability, BRAF mutation and KRAS mutation were all independent prognostic factors for colorectal cancer survival., We show for the first time that this important pediatric tumor may harbor the oncogenic BRAFV600E mutation, providing the first insights to their personalized treatment., In 19 cases of papillary tumor of the pineal region, there was a lack of BRAF-V600E mutations., BRAF overexpression is associated with BRAF V600E mutation in papillary thyroid carcinomas., BRAF mutation frequencies depended on histological subtype and localization of primary melanoma., Data suggest that the two strands of the BRAF promoter region, the G-rich strand and the C-rich strand, fold into a predominant antiparallel G-quadruplex and into an i-motif, respectively, and that they can coexist at nearly physiological conditions., Studies indicate that concurrent inhibition of proto-oncogene protein B-raf (BRAF) and Map kinase kinase (MEK) improved the most effective therapeutic modality as compared as single BRAF or MEK inhibition for patients with metastatic melanoma (MM)., Results show that active BRAF upregulates HMGCL via Oct-1 in cancer cells. HMGCL selectively promotes BRAF V600E-dependent phosphorylation and activation of MEK1 pathway by controlling intracellular levels of its product acetoacetate., v-raf murine sarcoma viral oncogene homolog B (BRAF) is preferentially mutated in proximal colon cancers., Report 3-fold increased risk of death for higher-risk melanomas harboring NRAS or BRAF mutations., BRAF mutations are associated with metastatic colorectal cancer., BRAF mutation detection in cell block material is feasible and highly specific for papillary thyroid carcinoma, Colon cancers from Asians have a lower rate of BRAF mutations than blacks or whites., The RAS-binding domain of human BRAF protein exhibits allosteric conformational changes upon binding HRAS., BRAF(V600E) mutation induces MGL ligand expression, thereby providing a direct link between oncogenic transformation and aberrant expression of immunosuppressive glycans in colorectal neoplasms., Retrospective analysis suggesting that nivolumab has similar efficacy and safety outcomes in patients with wild-type or mutant BRAF, regardless of prior BRAF inhibitor or ipilimumab treatment., real-time PCR cycle threshold values for the BRAFV600E mutation obtained from fine needle aspirates can be associated with central lymph node metastasis in papillary thyroid microcarcinoma patients, Report acute kidney injury in patients receiving BRAF inhibitors., Letter/Case Reports, Cytomorphologic features can help select nodules for the BRAF(V600E) mutation test among thyroid nodules read as "suspicious for malignancy" on cytology., Case Report, Studies indicate that more than half of all Erdheim-Chester disease (ECD) patients carry the proto-oncogene protein B-raf mutation BRAF(V600E) and treated with vemurafenib, a BRAF inhibitor, which has proven highly beneficial., BRAF Mutations are associated with Lung Adenocarcinoma., Findings suggest that triple therapy directed against BRAF/MEK/ErbB3 may be able to provide durable control of BRAF mutated metastatic melanoma., This study sought to investigate the correlations of V-raf murine sarcoma viral oncogene homolog B1 (BRAF) gene mutations with the clinicopathologic features of papillary thyroid carcinoma, BRAFV600E Mutation Status in obese Patient is associated with Papillary Thyroid Cancer., Results revealed that in patients with papillary thyroid microcarcinoma (PTMC), BRAF mutation is associated with tumor size, multifocality and aggressive features and may be used as a predictive factor for prognosis of PTMC. [meta-analysis], BRAF mutations are infrequent, whereas C-KIT and NRAS mutations are seen with higher frequency in vulvar melanomas than melanomas of other sites., BRAF mutations are associated with follicular variant of thyroid papillary carcinoma., Despite its high specificity, our meta-analysis shows that BRAF(V600E) mutation analysis has a low sensitivity in diagnosing papillary thyroid cancer in thyroid nodules, Compared with RAS or PAX8/PPARG-positive TCs, BRAFV600E or RET/PTC-positive Thyroid cancers were more often associated with stage III/IV disease and recurrence., neuregulin 1 promotes compensatory ErbB3 receptor signaling in mutant BRAF melanoma, BRAF V600E-mutated microcarcinomas represent a distinct biological subtype, Letter/Case Report, presence of BRAF mutations in melanoma associated with younger age, Data suggest that combination of proto-oncogene protein B-raf (BRAF) and mTOR serine-threonine kinase (mTOR) inhibition forms the basis of a treatment regimen of thyroid cancer., BRAF V600 appears to be a targetable oncogene in some, but not all, nonmelanoma cancers. Preliminary vemurafenib activity was observed in non-small-cell lung cancer and in Erdheim-Chester disease and Langerhans'-cell histiocytosis., NRASQ61R and BRAFV600E immunohistochemistry coupled with next-generation sequencing allow detection of mutations in melanoma challenging samples., BRAF codon 600 mutations not found in Iranian prostate adenocarcinoma patients., KRAS and BRAF oncogenes have roles in colorectal cancer development and therapy resistance [review], Report BRAF mutations in selected cohort of patients with pulmonary metastases of malignant melanoma and prognostic implications., BRAF mutations seem to occur exclusively in the epithelial, but not in the stromal component, BRAF fusions are rare driver alterations in a wide variety of malignant neoplasms, but enriched in Spitzoid melanoma, pilocytic astrocytomas, pancreatic acinar and papillary thyroid cancers., AKT3 has a role in prostate cancer proliferation through regulation of Akt, B-Raf, and TSC1/TSC2, The lesions designated as KAs and BRAF inhibitor-associated verrucous keratoses had a similar mutational profile., no BRAF V600E mutations were found in PMSAs, but KIAA1549-BRAF fusion was identified in intermediate pilomyxoid tumors, Report BRAF V600 mutation detection in a large cohort of clinical samples of cutaneous melanoma metastases to the lymph nodes., Tumors with non-V600E BRAF mutants are insensitive to these drugs., LY3009120 also inhibits various forms of RAF dimers including BRAF., 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, BRAF mutation is associated with melanoma., BRAF V600E mutation in non-tumoral surrounding tissue in patients with colorectal cancer may be used as a valuable marker to foresee clinical outcome or a possible recurrence., 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., 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., Case Report, Dual inhibition of BRAF(V600E) and MEK reduced but did not prevent SW1736 invasion., BRAF V600-Mutation is associated with Colorectal Cancer., A constitutive active MAPK/ERK pathway due to BRAFV600E mutation positively regulates aryl hydrocarbon receptor pathway in papillary thyroid carcinoma., consideration needs to put on multiple targets when deciding molecular target therapies for patients with BRAF V600E mutated thyroid carcinoma, Systems Analysis of Adaptive Responses to MAP Kinase Pathway Blockade in BRAF Mutant Melanoma., Case Report, BRAF-mutated conjunctival melanoma (CM) were frequent in younger patients and were rare in tumors involving the extrabulbar conjunctiva., BRAF Mutation is associated with response to therapy in Advanced Melanoma., Combination of a BRAF inhibitor plus a MEK inhibitor adds a clear benefit over monotherapy with BRAF inhibitor in unresectable or metastatic cutaneous BRAF Val600-mutation-positive melanoma., Among 33 BRAF wild-type colorectal carcinomas, 16 had no or weak staining, whereas 15 (45%) had heterogeneous staining. In contrast with colorectal carcinoma, Bond and Ventana VE1 IHC in melanoma and PTC were highly concordant with sequencing results, 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., Patients with multifocal PTC whose largest tumor is BRAF-negative can have smaller tumors that are BRAF-positive., PXA in adults PXA may present features distinct from pediatric PXA. Anaplastic features and BRAF mutation may potentially identify specific subgroups with distinct prognoses, BRAF V600-Mutation is associated with Colorectal Cancer., The presence or absence of the BRAF mutation and TERT promoter polymorphism was not significantly correlated with survival in Papillary thyroid carcinoma, Monoclonal antibody VE1 immunohistochemistry predicts BRAF V600E mutation status and clinical outcome in colorectal cancer., BRAFV600 mutations are associated with response to BRAF inhibitors in metastatic melanoma., BRAF mutation is frequent in early-onset colorectal cancer in Taiwan and is associated with a poorly differentiated histology, a serrated precursor polyp, focal signet ring cell differentiation, lack of microsatellite instability and a poor prognosis., B-Raf(V600E) mutation in metastatic melanoma cells up-regulated tissue factor expression on cell membranes and promoted thrombin production, Apart from these distinct Cdc37/Hsp90 interfaces, binding of the B-Raf protein kinase to the cochaperone is conserved between mammals and nematodes., BRAF mutation is associated with poor response to cetuximab in colorectal carcinoma., that BRAF sequencing has been used to discriminate between dedifferentiated papillary thyroid carcinoma and tumor to tumor metastasis, High frequency and specificity of the V600E BRAF mutation make it a useful biochemical marker for selecting the right surgical strategy for thyroidectomy., 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)., Vitamin C is selectively toxic to cells with mutant KRAS or BRAF alleles., Data indicate that mutations in PTEN phosphatase A167T and NRAS protein Q61L, and proto-oncogene protein BRAF V600E were detected in melanoma cell line., Case Report, The vast majority of these tumors harbor the oncogenic BRAF V600E mutation. [review], In the validation-set (508 pts, RAS wt, Cooperation of BRAF(F595L) and mutant HRAS is associated with histiocytic sarcoma., Characterization of TP53 as a downstream effector of miR-3151 provides evidence for a causal link between BRAF mutations and TP53 inactivation, 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., Chronic lymphocytic thyroiditis was an independent predictor for less aggressiveness in conventional papillary thyroid carcinoma patients regardless of BRAF mutation status., 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., Report incidence and heterogeneity of genetic changes driving BRAF inhibitor resistance in melanomas., Recent reports show a significant radiosensitization of the irradiated healthy tissue in patients with melanoma after the combination of radiotherapy and BRAF(V600) inhibitors, evoking concern in clinical practice, 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., identification of 7 BRAF-induced genes that are specific for BRAF V600E-driven papillary thyroid carcinoma., The presence of the BRAFV600E mutation is independently associated with high F-18 FDG uptake on preoperative PET/CT in patients with overt papillary thyroid cancer., Actin remodeling confers BRAF inhibitor resistance to melanoma cells through YAP/TAZ activation, BRAF V600E mutation is associated with Langerhans cell histiocytosis., The significant association of SLP-2 overexpression with unfavorable clinicopathological characteristics and BRAFV600E mutation indicates that SLP-2 may have a role in aggressiveness of BRAF-mutated papillary thyroid carcinoma., Findings suggested that BRAF-activated noncoding RNA may contribute to hepatocellular carcinoma initiation and progression., results reveal a common BRAF(V600E)-directed transcriptional regulatory pathway that mediates epigenetic silencing in unrelated solid tumors and provide strong support for an instructive model of oncoprotein-directed epigenetic silencing, Conclude that PRIMA-1(Met) through its ability to directly reactivate p53, sensitises (V600E/K)BRAF-positive melanoma cells to BRAF inhibitors., Letter, BRAF mutation is playing an important role in the pathogenesis of pyogenic granuloma., MC1R status is associated with BRAF(V600E), BRAF(V600K), and NRAS mutations in cutaneous melanomas, Colorectal poorly differentiated neuroendocrine carcinomas frequently harbor BRAF mutations and are associated with poor overall survival., Apart from BRAF V(600)E, no other recurrent somatic mutation was identified in these hairy cell leukaemia exomes, thereby excluding additional acquired mutations as also prevalent at a near-universal frequency in this form of the disease., The rate of the BRAF V600E mutation in the pediatric population with papillary thyroid carcinoma is significantly lower than that seen in the adult population, BRAF-V600E expression in primary nodular melanoma is associated with aggressive tumour features., This study demonstrated that when whole chromosome 7 gain accompanies the KIAA1549-BRAF fusion, the fusion likely arises first., beta3-alphaC deletions are activating mutations in BRAF. BRAF deltaNVTAP confers CRAF- and dimer-independent activity and is resistant to vemurafenib., BRAF inhibitor therapy-associated melanocytic lesions lack the BRAF V600E mutation and show increased levels of cyclin D1 expression., Low incidence of BRAF mutations in adenocarcinomas of the ampulla of Vater suggest no major role in tumorigenesis., the prevalence and clinicopathological associations of BRAF V600E and TERT promoter mutations in Chinese PTC patients, The BRAF-mutated Colorectal Cancers ,in comparison to KRAS-mutated ones, are associated with a much worse prognosis for the afflicted patients., MEK1 interacts with B-Raf.,
OFFICIAL_GENE_SYMBOL BRAF,
OMIM_DISEASE Cardiofaciocutaneous syndrome, Adenocarcinoma of lung, somatic, Noonan syndrome 7, LEOPARD syndrome 3, Colorectal cancer, somatic, Melanoma, malignant, somatic, Nonsmall cell lung cancer, somatic,
SP_COMMENT catalytic activity:ATP + a protein = ADP + a phosphoprotein., cofactor:Binds 2 zinc ions per subunit., disease:Defects in BRAF 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 BRAF are involved in a wide range of cancers., disease:Defects in BRAF are involved in lung cancer [MIM:211980]., disease:Defects in BRAF are involved in non-Hodgkin lymphoma (NHL) [MIM:605027]. NHL is a cancer that starts in cells of the lymph system, which is part of the body's immune system. NHLs can occur at any age and are often marked by enlarged lymph nodes, fever and weight loss., disease:Defects in BRAF may be a cause of colorectal cancer (CRC) [MIM:114500]., function:Involved in the transduction of mitogenic signals from the cell membrane to the nucleus. May play a role in the postsynaptic responses of hippocampal neuron., similarity:Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. RAF subfamily., similarity:Contains 1 phorbol-ester/DAG-type zinc finger., similarity:Contains 1 protein kinase domain., similarity:Contains 1 RBD (Ras-binding) domain., subunit:Interacts with RIT1., tissue specificity:Brain and testis.,
Raf-1 proto-oncogene, serine/threonine kinase(RAF1) Raf-1 proto-oncogene, serine/threonine kinase(RAF1) Related Genes Homo sapiens
CHROMOSOME 3,
CYTOBAND 3p25,
ENSEMBL_GENE_ID ENSG00000132155,
GENERIF_SUMMARY These data show that Ser-259 dephosphorylation contributes to Raf-1 activation by supporting its membrane accumulation rather than by increasing the specific activity of the kinase, PAK1 primes MEK1 for phosphorylation by Raf-1 kinase during cross-cascade activation of the ERK pathway., targeted expression inhibits juvenile myelomonocytic leukemia cell growth, effects of paclitaxel on Raf-1 phosphorylation in ovarian cancer cells, Results indicate that the phosphorylation of Ser(338) and Tyr(341) on Raf-1 exerts an important effect on reconfiguring the two MEK1-binding sites., These data suggest that GILZ contributes, through protein-to-protein interaction with Raf-1 and the consequent inhibition of Raf-MEK-ERK activation, to regulating the MAPK pathway and to providing a further mechanism underlying GCH immunosuppression., Raf activation increased the expression of cyclin A, cyclin D, cyclin E, and p21(Cip1), which are associated with G(1) progression, Activation of the ras/raf-1 signal transduction pathway leads to prominent phenotypic changes that resemble differentiation of gastrointestinal carcinoid cells in vitro., phosphorylation by p21-activated kinase 1 and Src regulates Raf-1 autoinhibition, c-Raf1 activation occurs without serine 338 phosphorylation, serum stimulation of fibroblasts in floating matrices does not result in ERK translocation to the nucleus and there was decreased serum activation of upstream members of the ERK signaling pathway, MEK and Raf., The 1,25(OH)(2)D3-responsive element in cystatin A gene is identical to TRE, T2 (-272 to -278). Suppression of Raf-1/MEK1/ERK1,2 signaling pathway increases cystatin A expression of normal human keratinocytes., Raf1 may have a role in antineoplastic drug resistance, Sprouty4 binds to Raf1 through its carboxy-terminal cysteine-rich domain, and this binding is necessary for the inhibitory activity of Sprouty4., findings implicate Raf-1 as a pivotal regulator of endothelial cell survival during angiogenesis, results show that raf-1 protein induction suppresses neuroendocrine marker and hormone production in human gastrointestinal carcinoid cells via a pathway dependent on MEK activation, Raf is regulated through phosphorylation and N terminus-C terminus interaction, a functional phosphatidate binding site is necessary for Raf-1 function in embryonic development, Raf-1 has a role in modulating integrin-stimulated ERK activation when bound to CAMKII, together, our data suggest that the synergistic activation of Raf-1 kinase in response to PMA and H(2)O(2) occurs via mechanisms that involve an interaction of Raf-1 kinase and PKC-epsilon., mutation analysis of the conserved regions in the RAF1 gene in human colorectal adenocarcinoma, Ovarian cancers demonstrate differential sensitivity to antisense oligonucleotides targeted against Raf-1, and target expression levels., Despite the effects of constitutively active Raf on pro-B cell expansion in Raf transgenic mice, Raf activation is not sufficient to rescue early B cell development in IL-7 receptor-deficient mice., RAF1 promotes herpesvirus 8 infection., 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., Raf1 kinase is released when it is hyperphosphorylated and activated during oxidative and other stresses, Raf1 and MAPK-activated protein kinase 2 are activated by L-ascorbic acid in acute myeloid leukemia cells., Raf1 potentiates drug-stimulated cyclic AMP accumulation in cells expressing adenyl cyclcase 6 after activation of multiple signaling pathways., Raf-1 links mitogenic signaling to Retinoblastoma Protein and that disruption of this interaction could aid in controlling proliferative disorders, findings indicate that ligation of retinol to a specific site embedded in the regulatory domain is an important feature of c-Raf regulation in the redox pathway., proteomic analysis of Raf-1 signaling complexes was used to show that Raf-1 counteracts apoptosis by suppressing the activation of mammalian sterile 20-like kinase (MST2), a novel Ras-independent ERK1/2 activation system in which p110gamma/Raf-1/MEK1/2 and PKA/B-Raf/MEK1/2 cooperate to activate ERK1/2., The induction of the raf-1/MEK1 pathway blocks IGF-1-mediated intracellular neuroendocrine hormone regulation. This pathway may be a therapeutic target in gastrointestinal carcinoid tumor therapy., Raf-1 may be involved in angiogenesis by controlling the expression of angiogenesis-related factors; study provides a possible strategy for the treatment of tumor angiogenesis by targeting Raf-1, the HER2/Raf-1/AP-1 axis may promote the development of androgen insensitive prostate cancer, leading to early relapse, Role for caspase-9 mediated cleavage of Raf-1 in the negative feedback regulation of hematopoietic cell apoptosis induced by growth factor withdrawal., regulated by an N-terminal autoinhibitory domain whose actions are blocked by interaction with Ras, essential role of Ras-induced conformational change in mitogen-activated protein kinase kinase activation by c-Raf, activation is regulated by CNK1, Pak1-dependent Raf-1 phosphorylation regulates its mitochondrial localization, phosphorylation of BAD, and Bcl-2 association, Raf-1 phosphorylation on serine 338 (S338) is a critical step in EGF aktivation of ERK that is lost in nonadherent cells., Raf-1 may mediate its anti-apoptotic function by interrupting ASK1-dependent phosphorylation of ALG-2., Activation of raf-1 leads to cessation of cell growth and suppression of calcitonin and chromogranin A production, results suggest that activated JNK can, in turn, activate not only jun but also raf that, in turn, activates MEK that can then cross-activate JNK in a positive feedback loop, selective reduction in catalytic activity and expression of B-Raf but not Raf-1 suggest that B-Raf may be playing an important role in altered ERK signaling in brain of suicide subjects, and thus in the pathophysiology of suicide, PP2A ABalphaC and ABdeltaC holoenzymes function as positive regulators of Raf1-MEK1/2-ERK1/2 signaling by targeting Raf1, Coll I activates the ERK/MAP Kinase pathway in Jurkat T cells through the activation of Ras and Raf-1., Erbin has a regulatory role in the Ras-Raf-MEK pathway and may inhibit ERK activation by disrupting the Sur-8-Ras/Raf interaction, data suggest that Raf-1 is the predominant Raf isoform responsible for regulating cellular growth in ovarian cancer cells and may be particularly important in high grade serous ovarian cancers, Data suggest that B-RAF activates C-RAF through a mechanism involving 14-3-3 mediated heterooligomerization and C-RAF transphosphorylation., inhibition of Raf-1 using an antisense raf oligonucleotide (AS-raf-ODN) to identify downstream targets of Raf-1 using microarray gene expression analysis, Merlin and MLK3 can interact in situ and merlin can disrupt the interactions between B-Raf and Raf-1 or those between MLK3 and either B-Raf or Raf-1., CD44 interaction with LARG and EGFR plays a pivotal role in Rho/Ras co-activation, PLC epsilon-Ca2+ signaling, and Raf/ERK up-regulation required for CaMKII-mediated cytoskeleton function and in head and neck squamous cell carcinoma progression, 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, Rodent and human tumor cells containing constitutively activated Raf/Raf/MEK/ERK pathways were resistant to mda-5-induced killing., This work provides new insight into how the cell microenvironment may influence Raf-1 expression to modulate cell-Fibronectin interactions in 3D., Rheb has a central role in the regulation of the Ras/B-Raf/C-Raf/MEK signaling network, Nicotine induces cell proliferation by beta-arrestin-mediated activation of the Src and Rb-Raf-1 pathways om ;img camcer., These findings support the thesis that Raf-1 signals cell proliferation and cell differentiation through different intermediary proteins., findings identify MEK/ERK as a new signaling pathway activated by NPM/ALK and indicate that the pathway represents a novel therapeutic target in the ALK-induced malignancies, These findings support a role of Slug in mediating Raf 1-induced transcriptional repression of occludin and subsequent epithelial to mesenchymal transition., These studies identify XIAP as a new substrate of Raf-1., cAMP suppresses CRAF in melanocytes. This suppresses the oncogenic potential of CRAF. When RAS is mutated in melanoma, the cells switch their signaling from BRAF to CRAF, dysregulating cAMP signaling & allowing CRAF to signal to MEK., Based on these findings, we speculate that Raf-1 is activated to effectively mediate Ras-dependent signals in Alzheimer's disease., The Raf kinase inhibitory protein (RKIP) binds to Raf-1 interfering with binding of the MEK substrate and potentially also Raf-1 activation., Data suggest that Raf-1 may interfere with the role of Rad24 by competing with Rad24 for binding to Cdc25 or a direct phosphorylation of Cdc25, bypassing the checkpoint pathway in DNA repair through Cdc25 activation., in human airway smooth muscle cells, The interaction between eEF-1A and C-Raf increases eEF-1A stability and induces a survival activity., The results suggest that multiple cellular signaling pathways can reactivate the virus in a genetically homogeneous cell population. Further analysis revealed that the Raf/MEK/ERK/Ets-1 pathway mediates Ras-induced reactivation., Hepatitis B virus X protein stimulates the mitochondrial translocation of Raf-1 via oxidative stress, different pathogens (ie. Mycobacterium tuberculosis, M. leprae, Candida albicans, measles virus, and HIV-1) interacted with DC-SIGN to activate the Raf-1-acetylation-dependent signaling pathway to modulate signaling by different TLRs, results show overexpression of RAF-1 in mantle cell leukemia compared with tonsilar B-lymphocytes, Study identified 5 mutations in RAF1 in 10 individuals with Noonan syndrome; those with mutations causing changes in the CR2 domain of RAF1 had hypertrophic cardiomyopathy, while those with mutations leading to changes in the CR3 domain did not., Study reports that 18 of 231 individuals with Noonan syndrome and 2 of 6 individuals with LEOPARD syndrome without PTPN11 mutations have missense mutations in RAF1, which encodes a serine-threonine kinase that activates MEK1 and MEK2., Raf-1 may interfere with the role of Rad24 by competing with Rad24 for binding to Cdc25 in DNA repair, bypassing the checkpoint pathway through Cdc25 activation., 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., reveal a paradigm of spatial regulation of Raf kinase by RKTG via sequestrating Raf-1 to the Golgi apparatus and thereby inhibiting the ERK signaling pathway, A pathway comprising PKCs>Raf-1>MEK-1>ERK-1/-2 mediates the effect of gastrin on the CgA promoter, and strongly suggests that enhanced phosphorylation of Sp1 and CREB is crucial for CgA transactivation through the G protein-coupled CCK-B/gastrin receptor., activated Ras, Golgi apparatus-localized Lck is needed for the full activation of Raf-1, Raf-1 in beta-cells led to a striking loss of Bad phosphorylation at serine 112 and an increase in the protein levels of both Bad and Bax, GRP78 may stabilize Raf-1 to maintain mitochondrial permeability and thus protect cells from endoplasmic reticulum stress-induced apoptosis., These results suggest that 0.05 Gy of ionizing radiation stimulates cell proliferation through the transient activation of Raf and Akt in CCD-18 Lu cells., Loss-of-function RKIP mutants still appear to bind to Raf-1. However the stability of the complexes formed between mutants and the N-region Raf-1 phosphopeptide were drastically reduced., These results suggest that oncogenic ras-p21 induces phosphorylation of both raf-Ser259 and Ser338 and that raf-Ser 259 phosphorylation may be effected by activated JNK., C-RAF is the only isoform that directly binds mitochondria, PAK5 is a potent regulator of Raf-1 activity and may control Raf-1 dependent signaling at mitochondria, Increased Raf-1 kinase is associated with glioma formation, the Rb/Raf-1 interaction has a role in cell proliferation and angiogenesis, RAS signaling in colorectal carcinomas through alteration of RAS, RAF, NF1, and/or RASSF1a., AhR is a master regulator of c-raf and propose cross-talk between AhR and the mitogen-activated protein kinase signaling pathway., The state of activation of components of mTOR, Ras/Raf kinase/ERK, and nuclear factor (NF)-kappaB signal transduction pathways, as well as cell cycle protein analyte correlates in gastric adenocarcinoma cases, was examined., study identified a group of melanomas with low-activity BRAF mutations (G469E- and D594G) that are reliant upon CRAF-mediated survival activity, phosphatidate promotes ERK phosphorylation in intact cells but does not activate Raf in vitro, the molecular interactions of arrestin2 and arrestin3 and their individual domains with the components of the two MAPK cascades, ASK1-MKK4-JNK3 and c-Raf-1-MEK1-ERK2, These data show an unexpected role of XIAP and cellular-inhibitor of apoptosis proteins in the turnover of C-RAF protein, thereby modulating the MAPK signalling pathway and cell migration., Mutations in the RAF1 are associated with Noonan syndrome., RAF may induce cell proliferation through hypermethylation of tumor suppressor gene p16INK4A, Alpha-adducin and Raf-1 kinase are redistributed and localized to the inclusion membrane in Chlamydia and Chlamydophila infected cells., Vitamin D3-triggered differentiation of human myeloid leukemia cells depends on downregulation of Akt, which dissociates from Raf1 and activates MAPK signaling., dectin-1 activates two independent signaling pathways, one through Syk and one through Raf-1, to induce immune responses., Results identify a nuclear redistribution of Raf1 during the retinoic acid-induced differentiation of HL-60 cells., loss of RKIP is a functional somatic event in carriers of C-RAF germline mutations, which contributes to the development of t-AML, Oncogenic RAF1 rearrangement and a novel BRAF mutation as alternatives to KIAA1549, GILZ1 and SGK1 provide a physical and functional link between the PI3K- and Raf-1-dependent signaling modules, Targeting NRAS alone or both BRAF and CRAF in combination or both BRAF and PIK3CA together showed delay in tumor growth., Phosphorylation of S621 turns over rapidly and is enriched in the activated pool of endogenous Raf-1., Data show that sorafenib inhibited the raf/ MEK/ERK signal pathway, and downregulated cyclin D1 and Rb levels., 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., DGKeta acts as a novel critical regulatory component of the Ras/B-Raf/C-Raf/MEK/ERK signaling cascade via a previously unidentified mechanism., DC-SIGN was constitutively associated with a signalosome complex consisting of the scaffold proteins LSP1, KSR1 and CNK and the kinase Raf-1., The C-Raf expression is up-regulated in a subset of melanomas but not in nevi, suggesting that it might be a valuable diagnostic marker and therapeutic target., Studies provide models for Ras in association with Raf kinase, RalGDS and PI3Kalpha and PI3Kgamma., 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., analysis of molecular pertubations allowing dysplasia to progress further to adenocarcinoma induced by exaggerted c-Raf kinase activity, Thus, the short hairpin-looped ODN-Raf, targeting the same region of c-raf-1 as miR-125b, is a multifunctional molecule reducing the expression of oncoproteins and stimulating cell death., Bcl-2-associated anthanogene 1 (BAG-1)'s effects were associated with an activation of RAF-1-a known binding partner of BAG-1, enhanced signaling through the MAP kinase pathway and a decrease in BIM expression., Data show that RAF not only neutralizes BAD's pro-apoptotic activity but activates it for a new function as a pore., Data show that melanoma cells expressing B-Raf(V600E) display a reduced C-Raf, Noonan syndrome (NS) is an autosomal dominant disorder caused by mutations in several proteins, including RAF1, which may later involve tumor onsets., dephosphorylation of S259 is the primary pathogenic mechanism in the activation of RAF1 mutants located in the CR2 domain as well as of downstream ERK, Results indicate that the Shoc2 scaffold protein modulates Ras-dependent Raf1 activation in a Ca(2+)- and calmodulin-dependent manner., Data show T117/T384 as Akt phosphorylation sites in MST2, and mutation of these sites inhibited MST2 binding to Raf-1 but enhanced binding to RASSF1A, accentuating downstream c-jun N-Terminal Kinase and p38 MAPK signaling and promoting apoptosis., Study demonstrates that human TAP-1 regulates signaling in vertebrate cells, acting at a previously uncharacterized step of the Ras pathway by inhibiting the ability of Raf to translocate to activated Ras at the cell membrane., Infection with Chlamydia trachomatis led to the Akt-dependent, increased phosphorylation (and inactivation) of Raf-1 at serine-259., Raf-1 was dominant in terms of promoting both cell cycle progression and preventing apoptosis when compared to Akt-1, Based on our results, it is possible that a subtle dysfunction (expression) of the RAF1 gene is involved in the development of the most common male reproductive tract disorder - unilateral or bilateral cryptorchidism, 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, 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., Findings suggest that modulating the C-RAFSer(259)/14-3-3 protein-protein interaction with a stabilizing small molecule may yield a novel potential approach for treatment of diseases resulting from an overactive Ras-RAF-MAPK pathway., Reduction in Raf-1 kinase inhibitory protein expression in gallbladder carcinoma contributes to invasion and metastasis and is a significant prognostic marker in patients with gallbladder carcinoma., Raf-1 over-expression was an independent prognostic factor of poor survival in hepatocellular carcinoma., JNK1, Raf-1 and Livin may be involved in the carcinogenesis of sporadic colorectal tubular adenoma., Hepatitis B virus could up-regulate Raf1 expression by enhancing the activity of its promoter in a dose-dependent manner, and HBs and HBx may be involved in this process., EZH2 expression-mediated downregulation of DNA damage repair leads to accumulation of recurrent RAF1 gene amplification in breast tumor initiating cells (BTICs), which activates p-ERK-beta-catenin signaling to promote BTIC expansion., 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., Studies indicate that Raf kinases are excellent molecular targets for anticancer therapy., Downregulation of RKIP increased the level of free Raf-1 and thereby elevated the mitochondrial translocation of Raf-1 during HBx-mediated hepatocarcinogenesis., The H-Ras-ERK-induced and HO-1-mediated pathway could protect renal cancer cells from apoptosis., study demonstrates a novel role of the Raf/MEK/ERK pathway in regulating AR expression in certain PCa types and provides an insight into PCa responses to its aberrant activation, Report cooperative effects of Akt-1 and Raf-1 on the induction of cellular senescence in doxorubicin or tamoxifen treated breast cancer cells., Protein arginine methyltransferase 5 regulates ERK1/2 signal transduction amplitude and cell fate through CRAF., These results demonstrate that replicative and oxidative stresses are not required for RAF-induced senescence, and this senescence is readily reversed upon loss of cyclin-dependent kinases., CRAF is required for mitotic progression. Phospho-Ser338 CRAF is upregulated in mitosis and localizes to the mitotic spindles in human cell lines and tumor biopsies., ndings demonstrate that Pak1 phosphorylates BAD directly at S111, but phosphorylated S112 through Raf-1., High RAF1 is associated with hepatocellular carcinoma., Conditional expression of oncogenic C-RAF in mouse pulmonary epithelial cells reveals differential tumorigenesis and induction of autophagy leading to tumor regression., Ras/Raf-1/MEK/ERK signal pathway is important for chemokine ligand CCL2-induced migration activity and matrix metalloproteinase (MMP)-9 expression., Cellular Raf-1 levels determine endometrial stromal cell motility and morphology., Data show that bilirubin interacts with the Raf/ERK/MAPK pathway, effect on cyclin D1 and Raf content, altered retinoblastoma protein profile of hypophosphorylation, calcium influx, and YY1 proteolysis., Raf-1/JNK /p53/p21 pathway may be involved in apoptosis, and NFkappaB1 may play a possible role in inhibiting apoptosis., LEOPARD syndrome, both with proven mutations in the RAF1 gene not previouslyreported, Interleukin-6, osteopontin and Raf/MEK/ERK signaling modulate the sensitivity of human myeloma cells to alkylphosphocholines., amplification of Raf1, MEK/MAPK oncogenic signaling during tumor growth promotes the genesis of metastatic lesions from primary tumors by activating the mesenchymal epithelial transition., RKIP expression may serve as a novel clinical biomarker in patients with esophageal squamous cell carcinoma., PP242 mTOR inhibitor activates ERK in multiple myeloma cells via a target of rapamycin complex 1 (TORC1)/eukaryotic translation initiation factor 4E (eIF-4E)/RAF pathway and activation is a mechanism of resistance, 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., unknown role for ML-IAP in controlling C-RAF stability and cell migration., These findings demonstrate that overexpression of Raf-1, p-Raf-1 or both could be considered as a new independent prognostic biomarker for poor survival rates for non-small cell lung cancer patients, Data indicate that erufosine caused dose-dependent decreases in the phosphorylation of PI3K (p85), Akt (PKB) at Thr 308 and cRaf in both MCF-7 and MDA-MB 231 cell lines., RAF1(D486N), as well as other kinase-impaired RAF1 mutants, showed increased heterodimerization with Braf, which was necessary and sufficient to promote increased MEK/ERK activation., Investigated BRAF and RAF1 alterations in Chinese prostate cancer.Found BRAF truncated in five of 200 informative Chinese cases & RAF1 was truncated in three of 204 informative cases and genomic rearrangements were correlated w/high Gleason scores., Gefitinib reverses the MDR protein gene expression and restores sensitivity of pancreatic cancer cells resistant to gemcitabine via RAF1/ERK signaling pathway., Determination of a 1, ARAF seems to stabilize BRAF, osteosarcoma patients whose tumors expressed raf-1 had a poorer clinical outcome than those whose tumors did not., SHOC2 and CRAF mediate ERK1/2 reactivation in mutant NRAS-mediated resistance to RAF inhibitor., results suggest a novel mechanism that the interaction of Raf-1 with cytoskeletal actin is critical for Raf-1 redistribution and airway smooth muscle cell proliferation during activation with the growth factor, The dominant effect of prolonged USP15 depletion upon signal amplitude is due to a decrease in CRAF levels while allowing for the possibility that USP15 may also function to dampen MAPK signaling through direct stabilization of BRAP., these findings establish RanBPM as a novel inhibitor of the ERK pathway through an interaction with the c-Raf complex and a regulation of c-Raf stability, DiRas3 interacts with C-RAF and downregulates MEK1 activity to restrict cell migration., Ras pathway activation via EGF treatment induced strong binding between B-Raf and C-Raf and a low level of binding between B-Raf and A-Raf., The ability of MEK to activate C-Raf was only partially dependent on MEK kinase activity but required MEK binding to C-Raf, suggesting that the binding results in a conformational change that increases C-Raf susceptibility to phosphorylation, Aberrant BRAF splice variants with deletions in both kinase and RAS-binding domains in rheumatoid arthritis patients demonstrate that these BRAF splice variants constitutively activate MAPK through CRAF, Antisense oligonucleotides targeting BCL-2 and C-RAF transcripts in tumor cell lines increases sensitivity to cytotoxic effect of etoposide., we identified multiple C-RAF mutations that produced biochemical and pharmacologic resistance in melanoma cell lines, Expression of miR-195 or knockdown of Raf-1 can similarly reduce tumor cell survival., activation of RAF1-MEK1-ERK/AKT axis may determine the resistance of non-small cell lung cancer cell lines bearing wild type EGFR to erlotinib, We hypothesize a potential direct or indirect role for SRC, RAF1, PTK2B genes in neurotransmission and in central nervous system signaling processes., 4 genes (EGFR, ERBB2, PTK2, and RAF1) with five SNPs (rs11238349, rs17172438, rs984654, rs11773818, and rs17172432) might be pivotal factors in the development of prostate cancer., 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., The higher expression of RAF1 mRNA and the activation of AKT/ERK proteins in vinorelbine-resistant non-small cell lung cancer cell lines may confer resistance to vinorelbine, A novel mechanism for response was discovered whereby high expression level of CAV-1 at the plasma membrane disrupts the BRaf/CRaf heterodimer and thus inhibits the activation of MAPK pathway during dasatinib treatment., analysis of RAF1 mutations in cohorts of South Indian, North Indian and Japanese patients with childhood-onset dilated cardiomyopathy, Authors demonstrate that the N-terminus of human Raf1 kinase (hRaf11-147aa) binds with human RKIP (hRKIP) at its ligand-binding pocket, loop "127-149", and the C-terminal helix by nuclear magnetic resonance experiments., Including several anti-apoptotic Bcl-2 family members and c-Raf., Results show that ubiquitination and levels of RAF-1 is controlled by both Shoc2 and HUWE1., These data suggest that miR-7-5p functions as a tumor suppressor gene to regulate glioblastoma microvascular endothelial cell proliferation potentially by targeting the RAF1 oncogene, Studied the promoter methylation and RNA expression profiles of ERK and RAF1 genes with risk of oral squamous cell carcinoma (OSCC) along with the promoter methylation status of ERK and RAF1 genes., our study demonstrated that miR-455-RAF1 may represent a new potential therapeutic target for colorectal carcinoma treatment., truncated RAF1 and BRAF proteins, recently described as products of genomic rearrangements in gastric cancer and other malignancies, have the ability to render neoplastic cells resistant to RTK-targeted therapy, approach identified 18 kinase and kinase-related genes whose overexpression can substitute for EGFR in EGFR-dependent PC9 cells, and these genes include seven of nine Src family kinase genes, FGFR1, FGFR2, ITK, NTRK1, NTRK2, MOS, MST1R, and RAF1., Aberrant expression of A-, B-, and C-RAF, and COT is frequent in PTC; increased expression of COT is correlated with recurrence of PTC., 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., Abnormal activation of the Ras/MAPK pathway may play a significant role in the development of pulmonary vascular disease in the subset of patients with Noonan syndrome and a specific RAF1 mutation., Data indicate that cyclic AMP signaling reduces the expression of sirtuin 6 deacetylase via inhibition of the c-Raf-MEK1-ERK1/2 pathway., Raf-1 may be an important biomarker in predicting the prognosis of chordoma patients., Suggest an interrelated kinase module involving c-Raf/PI3K/Lyn and perhaps Fgr functions in a nontraditional way during retinoic acid-induced maturation or during rescue of RA induction therapy using inhibitor co-treatment in RA-resistant leukemia cells., a model that CD166 regulates MCAM through a signaling flow from activation of PI3K/AKT and c-Raf/MEK/ERK signaling to the inhibition of potential MCAM ubiquitin E3 ligases, betaTrCP and Smurf1., DJ-1 directly binds to the kinase domain of c-Raf to stimulate its self-phosphorylation, followed by phosphorylation of MEK and ERK1/2 in EGF-treated cells., Besides mediating the anticancer effect, pDAPK(S308) may serve as a predictive biomarker for Raf inhibitors combination therapy, suggesting an ideal preclinical model that is worthy of clinical translation., This study provides the molecular basis for C-Raf C-terminal-derived phosphopeptide interaction with 14-3-3zeta protein and gives structural insights responsible for phosphorylation-mediated protein binding., Up-regulation of Raf-1 is associated with triple-negative breast cancer., our study suggested that black rice anthocyanins extract suppress metastasis in breast cancer cells by targeting the RAS/RAF/MAPK pathway, c-Raf interacts with MEK1 and activates MEK1 by phosphorylation.,
OMIM_DISEASE Noonan syndrome 5, LEOPARD syndrome 2, Cardiomyopathy, dilated, 1NN,
SP_COMMENT catalytic activity:ATP + a protein = ADP + a phosphoprotein., cofactor:Binds 2 zinc ions per subunit., disease:Defects in RAF1 are the cause of LEOPARD syndrome type 2 (LEOPARD syndrome-2) [MIM:611554]. LEOPARD syndrome is an autosomal dominant disorder allelic with Noonan syndrome. The acronym LEOPARD stands for lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormalities of genitalia, retardation of growth, and deafness., disease:Defects in RAF1 are the cause of Noonan syndrome type 5 (NS5) [MIM:611553]. Noonan syndrome (NS) 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., function:Involved in the transduction of mitogenic signals from the cell membrane to the nucleus. Part of the Ras-dependent signaling pathway from receptors to the nucleus. Protects cells from apoptosis mediated by STK3., PTM:Phosphorylated upon DNA damage, probably by ATM or ATR. Phosphorylation at Thr-269 increases its kinase activity., similarity:Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. RAF subfamily., similarity:Contains 1 phorbol-ester/DAG-type zinc finger., similarity:Contains 1 protein kinase domain., similarity:Contains 1 RBD (Ras-binding) domain., subunit:Interacts with Ras proteins; the interaction is antagonized by RIN1. Weakly interacts with RIT1 (By similarity). Interacts with STK3; the interaction inhibits its pro-apoptotic activity. Interacts with YWHAZ (unphosphorylated at 'Thr-232')., tissue specificity:In skeletal muscle, isoform 1 is more abundant than isoform 2.,