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BRAF V600E
GeneBRAF
Variantmissense
Amino Acid ChangeV600E
DNA Change (Coding Nucleotide)1799T>A
Transcript ID (GRCh37/hg19)ENST00000288602
Codon600
Exon15
Genomic Coordinates (GRCh37/hg19)7:140453136-140453136
COSMIC ID476
Germline/Somatic?Somatic
Pertinent Negative In
Tumor TypePrimary Site
MelanomaSkin
See All Pertinent Negatives

Interpretations

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Tier 1
BRAF
Variants
BRAF V600E
BRAF codon(s) 600 any
Primary Sites
Thyroid
Tumor Types
Papillary Carcinoma
Interpretation

Eighty percent of all thyroid cancers are papillary thyroid carcinomas (PTCs). BRAF is part of the mitogen-activated protein kinase (MAPK) signaling pathway and V600E is an activating mutation of BRAF. The BRAF V600E mutation has been reported in 45% of patients with papillary thyroid carcinoma. The BRAF V600E-like PTC's (BVL) and the RAS-like PTC (RL-PTC) are fundamentally different in their genomic, epigenomic, and proteomic profiles. Presence of a BRAF p.Val600Glu (V600E) mutation is highly specific for papillary thyroid carcinoma and is only rarely associated with the follicular variant PTC , other well-differentiated thyroid neoplasms or nodular goiters. The possible prognostic impact of BRAF V600E mutations in papillary carcinoma of the thyroid continues to be studied. FDA approved dabrafenib and trametinib administered together for the treatment of BRAF V600E mutation-positive anaplastic thyroid cancer.

Last updated: 2019-04-05 17:25:22 UTC
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Tier 1
BRAF
Variants
BRAF V600E
BRAF codon(s) 600 any
BRAF V600D
BRAF V600K
BRAF V600R
BRAF V600M
BRAF V600G
Primary Sites
Colon
Rectum
Tumor Types
Adenocarcinoma
Interpretation

Presence of a BRAF c.1799T>A, p.Val600Glu (V600E) mutation in a microsatellite unstable colorectal carcinoma indicates that the tumor is probably sporadic and not associated with Lynch syndrome (HNPCC). However, if a BRAF mutation is not detected, the tumor may either be sporadic or Lynch syndrome associated. Detection of BRAF mutations may also be useful in determining patient eligibility for anti-EGFR treatment. Approximately 8--15% of colorectal cancer (CRC) tumors harbor BRAF mutations. The presence of BRAF mutation is significantly associated with right-sided colon cancers and is associated with decreased overall survival. Some studies have reported that patients with metastatic CRC (mCRC) that harbor BRAF mutations do not respond to anti-EGFR antibody agents cetuximab or panitumumab in the chemotherapy-refractory setting. BRAF V600-mutated CRCs may not be sensitive to V600E targeted TKIs. Drug: Vemurafenib + Panitumumab, Encorafenib + Binimetinib + Cetuximab, Radiation + Trametinib + Fluorouracil

Last updated: 2018-03-15 21:07:15 UTC
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Tier 1
BRAF
Variants
BRAF V600E
BRAF codon(s) 600 any
BRAF V600D
BRAF V600K
BRAF V600R
BRAF V600M
BRAF V600G
Primary Sites
Skin
Tumor Types
Melanoma
Interpretation

B-RAF is a member of the RAF-family of kinases which plays an important role in the RAS-RAF-MEK-ERK mitotic signaling pathway. BRAF mutations are present in approximately 50% to 60% of cutaneous melanomas and are also present at lower frequencies in other melanoma subtypes. The hotspot for mutations in BRAF is at codon Val600 and the most common one is p.Val600Glu (V600E). Various B-Raf inhibitors(Vemurafenib, Dabrafenib) have been FDA approved for melanoma therapy in certain settings. Drug: Vemurafenib Dabrafenib Dabrafenib + Trametinib Vemurafenib + Cobimetinib Trametinib

Last updated: 2018-03-15 21:12:31 UTC
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Tier 1
BRAF
Variants
BRAF V600E
BRAF codon(s) 600 any
Primary Sites
Spinal Cord
Brain
Brain, Supratentorial
Brain, Infratentorial
Tumor Types
Glioblastoma
Pleomorphic Xanthoastrocytoma
Ganglioglioma
Neuroepithelial Neoplasm, NOS
Neuroepithelial neoplasm, high grade
Astrocytoma, NOS
Astrocytoma, Pilocytic
Interpretation

BRAF alterations have been described in a wide spectrum of brain tumors, including in gliomas and glioneuronal tumors. BRAFV600E mutations have been found in approximately 10--15% of pilocytic astrocytoma and in approximately 5--10% of pediatric diffusely infiltrating gliomas, including diffuse astrocytomas (WHO grade II), anaplastic astrocytomas (WHO grade III) and glioblastomas (WHO grade IV), but in less than 2% of comparable adult gliomas. This mutation is potentially targetable.

Last updated: 2018-09-18 14:47:52 UTC
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Tier 1
BRAF
Variants
BRAF V600E
BRAF codon(s) 600 any
Primary Sites
Bone
Lung
Bone Marrow
Lymph Node
Skin
Tumor Types
Langerhans Cell Histiocytosis
Histiocytic and Dendritic Cell Neoplasms
Interpretation

B-RAF is a member of the RAF-family of kinases which plays an important role in the RAS-RAF-MEK-ERK mitotic signaling pathway. Mutations of B-RAF have been described in up to 40-70% of Langerhans cell histiocytosis and approximately 50% of Erdheim-Chester disease. The hotspot for mutations in BRAF is at codon Val600 and these are activating mutations. The most common activating mutation is p.Val600Glu(V600E). Various B-Raf inhibitors(Vemurafenib, Dabrafenib) have been FDA approved for therapy for some tumor types in certain settings, and clinical trials for advanced BRAF V600 mutation-positive tumors using targeted therapy (often in combination with other therapy) may be available (clinical trials.gov).

Last updated: 2018-11-12 20:40:44 UTC
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Tier 2
BRAF
Variants
BRAF V600D
BRAF V600E
BRAF V600K
BRAF V600R
BRAF codon(s) 600 any
BRAF any mutation
Primary Sites
Blood
Bone Marrow
Tumor Types
Acute Leukemia of Unspecified Cell Type
Acute Myeloid Leukemia
Anemia, Unspecified
Atypical Chronic Myeloid Leukemia
B Lymphoblastic Leukemia/Lymphoma
Chronic Myeloid Leukemia
Chronic Myelomonocytic Leukemia
Chronic Neutrophilic Leukemia
Cytopenia
Eosinophilia
Essential Thrombocythemia
Leukocytosis
Leukopenia
Mast Cell Neoplasm
MDS with Ring Sideroblasts
Monocytosis
Myelodysplastic Syndrome
Myelodysplastic/Myeloproliferative Neoplasm
Myeloproliferative Neoplasm
Myeloid Neoplasm
Other Acute Leukemia
Polycythemia Vera
Polycythemia
Primary Myelofibrosis
T Lymphoblastic Leukemia/Lymphoma
Thrombocytopenia, Unspecified
Thrombocytosis
Chronic Lymphocytic Leukemia
Diffuse Large B Cell Lymphoma
Interpretation

B-RAF is a member of the RAF-family of kinases which plays an important role in the RAS-RAF-MEK-ERK mitotic signaling pathway. Mutations of B-RAF have been described in up to 100% of Hairy cell leukemia, 40-70% of Langerhans cell histiocytosis, approximately 50% of Erdheim-Chester disease, approximately 5% of diffuse large B cell lymphoma and plasma cell neoplasms and less than 5% of chronic lymphocytic leukemia. While some reports have found that 10-20% of cases of acute leukemias (ALL or AML) may have BRAF mutations, other reports have described no BRAF in those diseases or in myeloid diseases such as MDS or CML. The hotspot for mutations in BRAF is at codon Val600 and these are activating mutations. The most common activating mutation is p.Val600Glu(V600E). Various B-Raf inhibitors(Vemurafenib, Dabrafenib) have been FDA approved for therapy for some tumor types in certain clinical settings.

Last updated: 2018-11-12 20:40:44 UTC
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Tier 1
BRAF
Variants
BRAF V600E
Primary Sites
Brain
Tumor Types
Craniopharyngioma
Interpretation

Mutations in beta catenin (CTNNB1) are seen in about 90% of adamantinomatous craniopharyngiomas and mutations in BRAF (V600E) in papillary craniopharyngiomas. Adamantinomatous and papillary craniopharyngiomas have been shown to carry clonal mutations that are typically mutually exclusive but may occasionally coexist. These findings indicate that the adamantinomatous and papillary subtypes have distinct molecular underpinnings, each principally driven by mutations in a single well-established oncogene - CTNNB1 in the adamantinomatous form and BRAF in the papillary form, independent of age. This may have implications for the diagnosis and treatment of these tumors. Treatment with the BRAF inhibitor vemurafenib has been reported to result in disease stabilization in a patient with a papillary craniopharyngioma with a BRAF V600E mutation.

Last updated: 2020-07-24 14:53:53 UTC
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Tier 2
BRAF
Variants
BRAF V600E
Primary Sites
Kidney
Bladder
Ureter
Unknown
Tumor Types
Urothelial Carcinoma
Interpretation

BRAF is a member of the RAF-family of kinases which plays an important role in the RAS-RAF-MEK-ERK mitotic signaling pathway. BRAF V600E lies within the activation segment of the kinase domain of the BRAF protein and confers a gain of function. BRAF mutations are infrequent in urothelial carcinoma and are identified in 3-5% of cases. Various BRAF inhibitors (Vemurafenib, Dabrafenib) have been FDA approved for therapy for some tumor types in certain settings. The use of BRAF inhibitors in a number of other cancer types harboring BRAF V600E mutations are under investigation (clinicaltrials.gov). The clinicopathologic effects of BRAF in urothelial carcinoma remains to be fully elucidated.

Last updated: 2018-03-06 17:57:39 UTC
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Tier 2
BRAF
Variants
BRAF V600E
Primary Sites
Gall Bladder
Tumor Types
Adenocarcinoma
Interpretation

BRAF is a member of the RAF-family of kinases which plays an important role in the RAS-RAF-MEK-ERK mitotic signaling pathway. The hotspot for mutations in BRAF is at codon Val600 and these are activating mutations. The most common activating mutation is p.Val600Glu(V600E). BRAF mutation frequencies are highly controversial in biliary tract cancers ranging from 0 to 33% for BRAF V600E. As most studies with high BRAF mutation rates were performed on European cohorts, this has raised the question of whether these discordant results represent a regional difference in the genetics of biliary tract cancer. In large cohort of biliary tract cancers including intrahepatic cholangiocarcinomas, extrahepatic cholangiocarcinomas, and adenocarcinomas of the gallbladder, BRAF V600E mutations were only rarely found in intrahepatic cholangiocarcinomas and were not identified in any cases of gallbladder adenocarcinoma. The clinicopathologic significance of BRAF V600E remains to be further elucidated in adenocarcinoma of the gallbladder. Various BRAF inhibitors (Vemurafenib, Dabrafenib) have been FDA approved for therapy for some tumor types in certain settings. These results should be interpreted in the clinical and radiographic context.

Last updated: 2018-03-30 16:12:50 UTC
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Tier 1
BRAF
Variants
BRAF V600D
BRAF V600E
BRAF V600K
BRAF V600R
BRAF codon(s) 600 any
Primary Sites
Blood
Bone Marrow
Tumor Types
Hairy Cell Leukemia
Interpretation

B-RAF is a member of the RAF-family of kinases which plays an important role in the RAS-RAF-MEK-ERK mitotic signaling pathway. Mutations of B-RAF have been described in up to 100% of Hairy cell leukemia, 40-70% of Langerhans cell histiocytosis, approximately 50% of Erdheim-Chester disease, approximately 5% of diffuse large B cell lymphoma and plasma cell neoplasms and less than 5% of chronic lymphocytic leukemia. Some types of Hairy Cell Leukemia (eg, Hairy Cell Leukemia-Variant, Hairy Cell Leukemia with IgHV4-34 rearrangement) are negative for BRAF V600E mutation and may have MAP2K1 mutations. While some reports have found that 10-20% of cases of acute leukemias (ALL or AML) may have BRAF mutations, other reports have described no BRAF in those diseases or in myeloid diseases such as MDS or CML. The hotspot for mutations in BRAF is at codon Val600 and these are activating mutations. The most common activating mutation is p.Val600Glu(V600E). B-Raf inhibitors(eg, Vemurafenib) have been FDA approved for therapy for various tumor types and have been used in Hairy Cell Leukemia in some clinical settings, including in combination with other therapy.

Last updated: 2018-11-12 20:40:47 UTC
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Tier 2
BRAF
Variants
BRAF V600E
Primary Sites
Pancreas
Tumor Types
Adenocarcinoma
Interpretation

B-RAF is a member of the RAF-family of kinases which plays an important role in the RAS-RAF-MEK-ERK mitotic signaling pathway. The hotspot for mutations in BRAF is at codon Val600 and these are activating mutations. The most common activating mutation is p.Val600Glu(V600E). Various B-Raf inhibitors(Vemurafenib, Dabrafenib) have been FDA approved for therapy for some tumor types in certain settings, and clinical trials for advanced BRAF V600 mutation-positive tumors using targeted therapy (often in combination with other therapy) may be available (clinical trials.gov). It has been found that BRAF V600E has a mutation frequency of 2% in pancreatic cancer. A small study showed that no BRAF mutations were present in cases without KRAS mutations and in the few cases with BRAF mutations, a KRAS mutation was also present.

Last updated: 2019-01-22 18:26:32 UTC
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Tier 2
BRAF
Variants
BRAF V600E
Primary Sites
Lung
Tumor Types
Adenocarcinoma
Interpretation

BRAF is a member of the RAF-family of kinases which plays an important role in the RAS-RAF-MEK-ERK mitotic signaling pathway. The hotspot for mutations in BRAF is at codon Val600 and these are activating mutations. The most common activating mutation is p.Val600Glu(V600E). Activating BRAF(V600E) (Val600Glu) mutations have been identified in approximately 1-2% of lung adenocarcinomas. Various BRAF inhibitors (Vemurafenib, Dabrafenib, and Trametinib) have been FDA approved for therapy for some tumor types in certain clinical settings. Of note, Dabrafenib and Trametinib are approved for metastatic non-small cell lung cancer (NSCLC) harboring BRAF V600E mutations.

Last updated: 2019-01-22 18:29:57 UTC
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Tier 1
BRAF
Variants
BRAF V600E
Primary Sites
Thyroid
Tumor Types
Carcinoma
Interpretation

BRAF is part of the mitogen-activated protein kinase (MAPK) signaling pathway and V600E is an activating mutation of BRAF. The BRAF V600E mutation has been reported in 45% of patients with papillary thyroid carcinoma, which comprise 80 % of all thyroid cancers. Presence of a BRAF p.Val600Glu (V600E) mutation is highly specific for papillary thyroid carcinoma and is only rarely associated with the follicular variant PTC, other thyroid neoplasms, or nodular goiters. Anaplastic thyroid carcinomas are rare, highly aggressive, undifferentiated tumors that comprise 1% to 2% of all thyroid cancers in the United States. Well-differentiated papillary thyroid cancer, in which BRAF V600 mutations are an early and common driver mutation, precedes or coexists with approximately 50% of anaplastic thyroid carcinomas. Between 20% and 50% of anaplastic thyroid carcinomas harbor activating BRAF V600 mutations, with unknown prognostic significance. The possible prognostic impact of BRAF V600E mutations in carcinoma of the thyroid continues to be studied.

Last updated: 2019-05-23 22:43:59 UTC
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Tier 2
BRAF
Variants
BRAF V600E
Primary Sites
Larynx
Oral Cavity
Tumor Types
Squamous Cell Carcinoma
Interpretation

B-RAF is a member of the RAF-family of kinases which plays an important role in the RAS-RAF-MEK-ERK mitotic signaling pathway. Mutations of B-RAF have been described in <2% of head and neck squamous cell carcinomas. The hotspot for mutations in BRAF is at codon Val600 and the most common one is p.Val600Glu (V600E). Various B-RAF inhibitors have been FDA approved for cancer therapy in certain settings.

Last updated: 2019-01-22 18:51:59 UTC
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