Gene

BRAF

B-Raf proto-oncogene, serine/threonine kinase

Explore in graph →CI-GENE-00022038HGNC:1097 ENSG00000157764 NCBI 673 CIViC Cancer geneApproved

Curated evidence

Clinical evidence (574)

CIViC items involving this gene, grouped by molecular profile and therapy, with native levels and directions. 50 items per page.

civicCuratedShowing 101–150 of 574 evidence items · levels, directions and significance as curated at the source; each row links to its CIViC record.

Therapy	Cancer	Type	Level	Direction · significance	Rating (1–5)	Status	Evidence	Source
BRAF I462S1
(functional)	—UNRESOLVED	Functional	D	Supports Gain Of Function	3	submitted

Cohorts

Alteration frequency by cohort (200)

Frequency = cases affected / cases profiled within one cohort. Cohorts are never pooled.

cbioportalObserved200 cohort rows (showing 50, sorted by frequency) · frequency = affected / profiled, as published by each cohort; cohorts are not pooled. Hover a row badge for its release.

Cohort	Mapped cancer	Alteration	Affected (n)	Profiled (n)	Frequency (%)	Rank in cohort	Source
Metastatic Melanoma (MSK, JCO Precis Oncol 2017) skcm_vanderbilt_mskcc_2015	Cutaneous Melanoma	Ssm	66

Literature

Linked publications (142)

25 per page, newest first.

pubmedPublishedShowing 26–50 of 142 publications · bibliographic data as recorded by PubMed; abstracts are not reproduced.

Oncogenic AKAP9-BRAF fusion is a novel mechanism of MAPK pathway activation in thyroid cancer.
· J Clin Invest · 2005 · PMID 15630448 · validated civic_curation pubmed
Meta-analysis of BRAF mutation as a predictive biomarker of benefit from anti-EGFR monoclonal antibody therapy for RAS wild-type metastatic colorectal cancer.
· Br J Cancer · 2015 · PMID 25989278 · validated civic_curation pubmed
BRAF mutations in hairy-cell leukemia.
· N Engl J Med · 2011 · PMID 21663470 · validated civic_curation pubmed
Phase II Pilot Study of Vemurafenib in Patients With Metastatic BRAF-Mutated Colorectal Cancer.
· J Clin Oncol · 2015 · PMID 26460303 · validated civic_curation pubmed

BRAF intron 10 rearrangement2
Vemurafenib	Malignant NeoplasmALIAS	Predictive	C	Does Not Support Sensitivity Response	2	accepted	EID5974 The phase 2a MyPathway study assigned patients with HER2, EGFR, BRAF or SHH alterations to treatment with pertuzumab plus trastuzumab, erlotinib, vemurafenib, or vismodegib, respectively Of 26 patient… (full text at CIViC) PMID 29320312 · Hainsworth et al., 2018 · Open in CIViC	civic
Dabrafenib + VemurafenibSubstitutes	Melanoma	Predictive	B	Supports Resistance	3	accepted	EID6400 In a retrospective study of 44 relapsed melanoma patients harboring BRAF V600E or V600K (known BRAF inhibitor sensitizing mutations), MAPK pathway reactivation mechanisms were implicated in acquired r… (full text at CIViC) PMID 24265155 · Shi et al., 2014 · Open in CIViC	civic

BRAF intron 9 rearrangement2
Vemurafenib	Malignant NeoplasmALIAS	Predictive	C	Does Not Support Sensitivity Response	2	accepted	EID5973 The phase 2a MyPathway study assigned patients with HER2, EGFR, BRAF or SHH alterations to treatment with pertuzumab plus trastuzumab, erlotinib, vemurafenib, or vismodegib, respectively. Of 26 patien… (full text at CIViC) PMID 29320312 · Hainsworth et al., 2018 · Open in CIViC	civic
Dabrafenib + VemurafenibSubstitutes	Melanoma	Predictive	B	Supports Resistance	3	accepted	EID6401 In a retrospective study of 44 relapsed melanoma patients harboring BRAF V600E or V600K (known BRAF inhibitor sensitizing mutations), MAPK pathway reactivation mechanisms were implicated in acquired r… (full text at CIViC) PMID 24265155 · Shi et al., 2014 · Open in CIViC	civic

BRAF K601E6
(functional)	—UNRESOLVED	Functional	D	Supports Gain Of Function	5	submitted	EID12920 BRAF p.Lys601Glu (NM_004333.6:c.1801A>G) causes increased pERK/ERK ratio. PMID 15035987 · Wan et al., 2004 · Open in CIViC	civic
〃	—UNRESOLVED	Functional	D	Supports Gain Of Function	4	submitted	EID12921 BRAF p.Lys601Glu (NM_004333.6:c.1801A>G) causes increased phosphorylation of substrate of BRAF. PMID 28783719 · Yao et al., 2017 · Open in CIViC	civic
BRAF Inhibitor	Melanoma	Predictive	B	Does Not Support Sensitivity Response	4	submitted	EID7622 In a retrospective study from 20 institutes in 4 countries, the efficacy of BRAF inhibitor and/or MEK inhibitor in patients with melanoma harboring BRAF nonV600E/K mutations were evaluated. Treated wi… (full text at CIViC) PMID 31580757 · Menzer et al., 2019 · Open in CIViC	civic
Dabrafenib	Cutaneous MelanomaALIAS	Predictive	B	Supports Sensitivity Response	—	submitted	EID2812 In a study of 197 metastatic melanoma patients, BRAF mutations were identified in 95 patients including V600E (n=70), V600K (n=19), K601E (n=1) and D594N (n=1). Patients were treated with a specific R… (full text at CIViC) PMID 21343559 · Long et al., 2011 · Open in CIViC	civic
Vemurafenib	Malignant NeoplasmALIAS	Predictive	B	Does Not Support Sensitivity Response	3	submitted	EID5963 The phase 2a MyPathway study assigned patients with HER2, EGFR, BRAF or SHH alterations to treatment with pertuzumab plus trastuzumab, erlotinib, vemurafenib, or vismodegib, respectively. Of 26 patien… (full text at CIViC) PMID 29320312 · Hainsworth et al., 2018 · Open in CIViC	civic
Trametinib + VemurafenibSubstitutes	Cutaneous MelanomaALIAS	Predictive	D	Supports Sensitivity Response	3	accepted	EID1462 Preclinical study in 293H cell line. Ectopic expression of V600E, L597R/Q/S, and K601E mutants elevated phospho-MEK and ERK levels. Vemurafenib treatment of all of the BRAF mutant–expressing cells led… (full text at CIViC) PMID 22798288 · Dahlman et al., 2012 · Open in CIViC	civic

BRAF Kinase Domain Duplication3
(oncogenic)	Childhood Visual Pathway GliomaALIAS	Oncogenic	B	Supports Oncogenicity	4	submitted	EID12471 Fluorescence in situ hybridization (FISH) studies were performed using home brew probes targeting 3′ BRAF, 5′ BRAF, and a commercial CEP7 probe on 59 patients with optic nerve glioma. Duplication of t… (full text at CIViC) PMID 22892521 · Rodriguez et al., 2012 · Open in CIViC	civic
〃	Malignant Lung Neoplasm	Oncogenic	B	Supports Oncogenicity	4	submitted	EID12472 A total of 23,396 patients with lung cancer and comprehensive genomic profiling were reviewed for BRAF alterations, and kinase domain duplication (KDD) mutations were observed in 0.75% of the cases. F… (full text at CIViC) PMID 32913992 · Sheikine et al., 2018 · Open in CIViC	civic
Regorafenib	Acinar Cell CarcinomaALIAS	Predictive	C	Supports Sensitivity Response	4	submitted	EID12470 A 30 year old women with advanced acinic cell tumor of the right parotid gland had her disease progressed after initial systemic chemotherapy, followed by empirical erlotinib hydrochloride therapy. Pr… (full text at CIViC) PMID 26562024 · Klempner et al., 2016 · Open in CIViC	civic

BRAF L505H2
Vemurafenib	Melanoma	Predictive	B	Supports Resistance	3	accepted	EID1669 In this study, the investigators followed 10 patients treated with vemurafenib, and then they collected biopsies of lesions that progressed. In one of these patients, they identified the L505H mutatio… (full text at CIViC) PMID 25515853 · Hoogstraat et al., 2015 · Open in CIViC	civic
〃	Melanoma	Predictive	D	Supports Resistance	4	accepted	EID1668 Using a mutation screen in the BRAFV600E melanoma cell line A375, the L505H variant was identified as conferring resistance to vemurafenib. Analysis of the mutation in T293 cell lines found that the L… (full text at CIViC) PMID 24112705 · Wagenaar et al., 2014 · Open in CIViC	civic

BRAF L5974
(prognostic)	Malignant Colorectal NeoplasmCURATED_BROADER	Prognostic	B	Supports Poor Outcome	3	submitted	EID7476 Data from 117 patients with metastatic colorectal cancer (mCRC) harboring various BRAF mutations and 540 patients with mCRC harboring BRAF wild type were analyzed. BRAF mutation type was categorized t… (full text at CIViC) PMID 30967421 · Schirripa et al., 2019 · Open in CIViC	civic
BRAF Inhibitor	Melanoma	Predictive	B	Does Not Support Sensitivity Response	4	submitted	EID7621 In a retrospective study from 20 institutes in 4 countries, the efficacy of BRAF inhibitor and/or MEK inhibitor in patients with melanoma harboring BRAF nonV600E/K mutations were evaluated. Treated wi… (full text at CIViC) PMID 31580757 · Menzer et al., 2019 · Open in CIViC	civic
〃	Melanoma	Predictive	C	Supports Sensitivity Response	3	submitted	EID7626 In a retrospective study from 20 institutes in 4 countries, the efficacy of BRAF inhibitor and/or MEK inhibitor in patients with melanoma harboring BRAF nonV600E/K mutations were evaluated. Treated wi… (full text at CIViC) PMID 31580757 · Menzer et al., 2019 · Open in CIViC	civic
BRAF Inhibitor + Mitogen-Activated Protein Kinase Kinase InhibitorCombination	Melanoma	Predictive	B	Supports Sensitivity Response	3	submitted	EID7632 In a retrospective study from 20 institutes in 4 countries, the efficacy of BRAF inhibitor and/or MEK inhibitor in patients with melanoma harboring BRAF nonV600E/K mutations were evaluated. Treated wi… (full text at CIViC) PMID 31580757 · Menzer et al., 2019 · Open in CIViC	civic

BRAF L597Q3
Trametinib	Cutaneous MelanomaALIAS	Predictive	C	Supports Sensitivity Response	3	accepted	EID4905 Case study report including one patient with L597Q mutation-positive metastatic melanoma (M1b disease) treated with the MEK inhibitor trametinib. The L597Q patient achieved a RECIST partial response a… (full text at CIViC) PMID 24933606 · Bowyer et al., 2014 · Open in CIViC	civic
Vemurafenib	Malignant NeoplasmALIAS	Predictive	C	Does Not Support Sensitivity Response	2	accepted	EID5971 The phase 2a MyPathway study assigned patients with HER2, EGFR, BRAF or SHH alterations to treatment with pertuzumab plus trastuzumab, erlotinib, vemurafenib, or vismodegib, respectively. Of 26 patien… (full text at CIViC) PMID 29320312 · Hainsworth et al., 2018 · Open in CIViC	civic
Trametinib + VemurafenibSubstitutes	Cutaneous MelanomaALIAS	Predictive	D	Supports Sensitivity Response	2	accepted	EID1461 Preclinical study in 293H cell line. Ectopic expression of V600E, L597R/Q/S, and K601E mutants elevated phospho-MEK and ERK levels. Vemurafenib treatment of all of the BRAF mutant–expressing cells led… (full text at CIViC) PMID 22798288 · Dahlman et al., 2012 · Open in CIViC	civic

BRAF L597R3
(diagnostic)	Multinodular and Vacuolated Neuronal TumorALIAS	Diagnostic	C	Supports Positive	2	submitted	EID12459 In a 54-year-old female with chronic headache and a right temporal lobe MVNT, NGS (479-gene panel) identified a BRAF p.L597R mutation (NM_004333.6:c.1790T>G; VAF 5%). PMID 29428973 · Pekmezci et al., 2018 · Open in CIViC	civic
Vemurafenib	Melanoma	Predictive	C	Supports Sensitivity Response	4	accepted	EID728 A case report of a patient with BRAF L597R mutation and clinical response to BRAF-inhibition (Vemurafenib) that correlated to in-vitro models. PMID 23715574 · Bahadoran et al., 2013 · Open in CIViC	civic
Trametinib + VemurafenibSubstitutes	Cutaneous MelanomaALIAS	Predictive	D	Supports Sensitivity Response	2	accepted	EID1458 Preclinical study in 293H cell line. Ectopic expression of V600E, L597R/Q/S, and K601E mutants elevated phospho-MEK and ERK levels. Vemurafenib treatment of all of the BRAF mutant–expressing cells led… (full text at CIViC) PMID 22798288 · Dahlman et al., 2012 · Open in CIViC	civic

BRAF L597S2
MEK Inhibitor REC-4881	Cutaneous MelanomaALIAS	Predictive	C	Supports Sensitivity Response	3	accepted	EID1460 Case report of a 69 year old patient with metastatic melanoma treated with MEK inhibitor TAK-733 in a clinical trial. A partial radiographic response with a decrease of 31% in the sum of maximum diame… (full text at CIViC) PMID 22798288 · Dahlman et al., 2012 · Open in CIViC	civic
Trametinib + VemurafenibSubstitutes	Cutaneous MelanomaALIAS	Predictive	D	Supports Sensitivity Response	2	accepted	EID1459 Preclinical study in 293H cell line. Ectopic expression of V600E, L597R/Q/S, and K601E mutants elevated phospho-MEK and ERK levels. Vemurafenib treatment of all of the BRAF mutant–expressing cells led… (full text at CIViC) PMID 22798288 · Dahlman et al., 2012 · Open in CIViC	civic