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 551–574 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 Fusion10
PLX4720 + VemurafenibSubstitutes	Childhood Low Grade Glioma	Predictive	D	Supports Adverse Response	4

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 1–25 of 142 publications · bibliographic data as recorded by PubMed; abstracts are not reproduced.

Improved survival with vemurafenib in melanoma with BRAF V600E mutation.
· N Engl J Med · 2011 · PMID 21639808 · validated civic_curation pubmed
Improved overall survival in melanoma with combined dabrafenib and trametinib.
· N Engl J Med · 2015 · PMID 25399551 · validated civic_curation pubmed
Cobimetinib combined with vemurafenib in advanced BRAF(V600)-mutant melanoma (coBRIM): updated efficacy results from a randomised, double-blind, phase 3 trial.
· Lancet Oncol · 2016 · PMID 27480103 · validated civic_curation pubmed
Encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF-mutant melanoma (COLUMBUS): a multicentre, open-label, randomised phase 3 trial.
· Lancet Oncol · 2018 · PMID 29573941 · validated

BRAF Fusion1
Vemurafenib	Malignant NeoplasmALIAS	Predictive	C	Does Not Support Sensitivity Response	2	accepted	EID5975 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

BRAF Fusion1

Vemurafenib

Malignant NeoplasmALIAS

Predictive

Does Not Support Sensitivity Response

accepted

EID5975

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

BRAF Fusion1
BRAF Inhibitor + TunlametinibSubstitutes	Langerhans Cell Histiocytosis	Predictive	D	Supports Sensitivity Response	3	submitted	EID8030 Novel BRAF gene fusion in Langerhans Cell Histiocytosis lesions results in constitutive ERK activation that is responsive to second-generation BRAF and MEK inhibitors, but not to a BRAF-V600E inhibito… (full text at CIViC) PMID 27729324 · Chakraborty et al., 2016 · Open in CIViC	civic

BRAF Fusion1

BRAF Inhibitor + TunlametinibSubstitutes

Langerhans Cell Histiocytosis

Predictive

Supports Sensitivity Response

submitted

EID8030

Novel BRAF gene fusion in Langerhans Cell Histiocytosis lesions results in constitutive ERK activation that is responsive to second-generation BRAF and MEK inhibitors, but not to a BRAF-V600E inhibito… (full text at CIViC)

PMID 27729324 · Chakraborty et al., 2016 · Open in CIViC

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BRAF D594G + BRAF V600E + KRAS MutationBRAF KRAS1
Cetuximab + ChemotherapyCombination	Colorectal Adenocarcinoma	Predictive	B	Does Not Support Sensitivity Response	3	submitted	EID11060 The Medical Research Council (MRC) COIN trial consisted of patients with histologically confirmed adenocarcinoma of the colon or rectum, inoperable metastatic or locoregional measurable disease, and w… (full text at CIViC) PMID 21641636 · Maughan et al., 2011 · Open in CIViC	civic

BRAF D594G + BRAF V600E + KRAS MutationBRAF KRAS1

Cetuximab + ChemotherapyCombination

Colorectal Adenocarcinoma

Predictive

Does Not Support Sensitivity Response

submitted

EID11060

The Medical Research Council (MRC) COIN trial consisted of patients with histologically confirmed adenocarcinoma of the colon or rectum, inoperable metastatic or locoregional measurable disease, and w… (full text at CIViC)

PMID 21641636 · Maughan et al., 2011 · Open in CIViC

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BRAF Mutation + KRAS Mutation + NRAS MutationKRAS NRAS BRAF2
(prognostic)	Colorectal Adenocarcinoma	Prognostic	B	Supports Poor Outcome	4	submitted	EID11061 The Medical Research Council (MRC) COIN trial consisted of patients with histologically confirmed adenocarcinoma of the colon or rectum, inoperable metastatic or locoregional measurable disease, and w… (full text at CIViC) PMID 21641636 · Maughan et al., 2011 · Open in CIViC	civic
Lifirafenib	Solid NeoplasmCURATED_BROADER	Predictive	B	Supports Sensitivity Response	2	submitted	EID12641 In a first in human open label phase 1 dose escalation and expansion study of lifirafenib in advanced solid tumors (NCT02610361; n = 131; BRAF-mutated n = 53, KRAS/NRAS-mutated n = 66; biomarker BRAF … (full text at CIViC) PMID 32182156 · Desai et al., 2020 · Open in CIViC	civic

BRAF Mutation + KRAS Mutation + NRAS MutationKRAS NRAS BRAF2

(prognostic)

Colorectal Adenocarcinoma

Prognostic

Supports Poor Outcome

submitted

EID11061

PMID 21641636 · Maughan et al., 2011 · Open in CIViC

civic

Lifirafenib

Solid NeoplasmCURATED_BROADER

Predictive

Supports Sensitivity Response

submitted

EID12641

In a first in human open label phase 1 dose escalation and expansion study of lifirafenib in advanced solid tumors (NCT02610361; n = 131; BRAF-mutated n = 53, KRAS/NRAS-mutated n = 66; biomarker BRAF … (full text at CIViC)

PMID 32182156 · Desai et al., 2020 · Open in CIViC

civic

BRAF G466V + NRAS Q61KNRAS BRAF2
Cetuximab	Malignant NeoplasmALIAS	Predictive	D	Supports Resistance	3	submitted	EID12450 Expression of mutant (Q61K) but not wildtype NRAS in the non-small cell lung carcinoma cell line, H1666 (BRAF G466V), resulted in reduced sensitivity to cetuximab as measured by cell growth and RAS-GT… (full text at CIViC) PMID 28783719 · Yao et al., 2017 · Open in CIViC	civic
Trametinib	Malignant NeoplasmALIAS	Predictive	D	Does Not Support Resistance	3	submitted	EID12451 Expression of mutant (Q61K) but not wildtype NRAS in the non-small cell lung carcinoma cell line, H1666 (BRAF G466V), resulted in reduced sensitivity to cetuximab but not trametinib as measured by cel… (full text at CIViC) PMID 28783719 · Yao et al., 2017 · Open in CIViC	civic

BRAF G466V + NRAS Q61KNRAS BRAF2

Cetuximab

Malignant NeoplasmALIAS

Predictive

Supports Resistance

submitted

EID12450

Expression of mutant (Q61K) but not wildtype NRAS in the non-small cell lung carcinoma cell line, H1666 (BRAF G466V), resulted in reduced sensitivity to cetuximab as measured by cell growth and RAS-GT… (full text at CIViC)

PMID 28783719 · Yao et al., 2017 · Open in CIViC

civic

Trametinib

Malignant NeoplasmALIAS

Predictive

Does Not Support Resistance

submitted

EID12451

Expression of mutant (Q61K) but not wildtype NRAS in the non-small cell lung carcinoma cell line, H1666 (BRAF G466V), resulted in reduced sensitivity to cetuximab but not trametinib as measured by cel… (full text at CIViC)

PMID 28783719 · Yao et al., 2017 · Open in CIViC

civic

BRAF Fusion1
Trametinib	Transitional Cell Carcinoma	Predictive	C	Supports Sensitivity Response	3	accepted	EID7763 In a case report, a patient with metastatic urothelial carcinoma harboring an NRF1-BRAF fusion was treated with trametinib. After two and a half months of treatment, MRI revealed 48.4% decrease in siz… (full text at CIViC) PMID 31010895 · Isaacson et al., 2019 · Open in CIViC	civic

BRAF Fusion1

Trametinib

Transitional Cell Carcinoma

Predictive

Supports Sensitivity Response

accepted

EID7763

In a case report, a patient with metastatic urothelial carcinoma harboring an NRF1-BRAF fusion was treated with trametinib. After two and a half months of treatment, MRI revealed 48.4% decrease in siz… (full text at CIViC)

PMID 31010895 · Isaacson et al., 2019 · Open in CIViC

civic

BRAF Fusion2
Trametinib	Melanoma	Predictive	D	Supports Sensitivity Response	3	accepted	EID726 BRAF-fusion in "pan-negative" melanomas were identified in TCGA data. Cell-lines with a PAPSS1-BRAF fusion were resistant to treatment with Vemurafenib but sensitive to treatment with Trametinib. This… (full text at CIViC) PMID 24345920 · Hutchinson et al., 2013 · Open in CIViC	civic
Vemurafenib	Melanoma	Predictive	D	Supports Resistance	3	accepted	EID725 BRAF-fusion in "pan-negative" melanomas were identified in TCGA data. Cell-lines with PAPSS1-BRAF fusion were resistant to treatment with Vemurafenib. PMID 24345920 · Hutchinson et al., 2013 · Open in CIViC	civic

BRAF Fusion2

Trametinib

Melanoma

Predictive

Supports Sensitivity Response

accepted

EID726

BRAF-fusion in "pan-negative" melanomas were identified in TCGA data. Cell-lines with a PAPSS1-BRAF fusion were resistant to treatment with Vemurafenib but sensitive to treatment with Trametinib. This… (full text at CIViC)

PMID 24345920 · Hutchinson et al., 2013 · Open in CIViC

civic

Vemurafenib

Melanoma

Predictive

Supports Resistance

accepted

EID725

BRAF-fusion in "pan-negative" melanomas were identified in TCGA data. Cell-lines with PAPSS1-BRAF fusion were resistant to treatment with Vemurafenib.

PMID 24345920 · Hutchinson et al., 2013 · Open in CIViC

civic

BRAF Fusion1
Trametinib	Cutaneous MelanomaALIAS	Predictive	C	Supports Sensitivity Response	2	accepted	EID1570 Case report of a 47year old female patient with metastatic melanoma (BRAF, NRAS, KIT negative). A PPFIBP2-BRAF fusion was identified from DNA from a brain metastasis (inton 3 of PPFIBP2 fused to intro… (full text at CIViC) PMID 26072686 · Menzies et al., 2015 · Open in CIViC	civic

BRAF Fusion1

Trametinib

Cutaneous MelanomaALIAS

Predictive

Supports Sensitivity Response

accepted

EID1570

Case report of a 47year old female patient with metastatic melanoma (BRAF, NRAS, KIT negative). A PPFIBP2-BRAF fusion was identified from DNA from a brain metastasis (inton 3 of PPFIBP2 fused to intro… (full text at CIViC)

PMID 26072686 · Menzies et al., 2015 · Open in CIViC

civic

BRAF Fusion2
Trametinib	Melanoma	Predictive	D	Supports Sensitivity Response	3	accepted	EID727 A TRIM24-BRAF fusion was identified in a single patient with metastatic melanoma that was "pan-negative" for driver mutations. A cell-line (293H) ectopically expressing the TRIM24-BRAF fusion was foun… (full text at CIViC) PMID 24345920 · Hutchinson et al., 2013 · Open in CIViC	civic
Vemurafenib	Cutaneous MelanomaALIAS	Predictive	D	Supports Resistance	3	accepted	EID1416 Foundation One NGS assay and targeted RNAseq identified PAPSS1-BRAF fusion in a melanoma sample. Further BRAF fusions (TRIM24-BRAF) were identified in TCGA and additional samples. Ectopic expression o… (full text at CIViC) PMID 24345920 · Hutchinson et al., 2013 · Open in CIViC	civic

BRAF Fusion2

Trametinib

Melanoma

Predictive

Supports Sensitivity Response

accepted

EID727

A TRIM24-BRAF fusion was identified in a single patient with metastatic melanoma that was "pan-negative" for driver mutations. A cell-line (293H) ectopically expressing the TRIM24-BRAF fusion was foun… (full text at CIViC)

PMID 24345920 · Hutchinson et al., 2013 · Open in CIViC

civic

Vemurafenib

Cutaneous MelanomaALIAS

Predictive

Supports Resistance

accepted

EID1416

Foundation One NGS assay and targeted RNAseq identified PAPSS1-BRAF fusion in a melanoma sample. Further BRAF fusions (TRIM24-BRAF) were identified in TCGA and additional samples. Ectopic expression o… (full text at CIViC)

PMID 24345920 · Hutchinson et al., 2013 · Open in CIViC

civic

BRAF Fusion1
Trametinib	Melanoma	Predictive	C	Supports Sensitivity Response	3	accepted	EID1663 Analysis of BRAF fusions in 20,573 tumors, across 12 distinct tumor types. BRAF fusions were identified in 55 (0.3%) patients and enriched in spitzoid melanoma, pilocytic astrocytomas, pancreatic acin… (full text at CIViC) PMID 26314551 · Ross et al., 2016 · Open in CIViC	civic

BRAF Fusion1

Trametinib

Melanoma

Predictive

Supports Sensitivity Response

accepted

EID1663

Analysis of BRAF fusions in 20,573 tumors, across 12 distinct tumor types. BRAF fusions were identified in 55 (0.3%) patients and enriched in spitzoid melanoma, pilocytic astrocytomas, pancreatic acin… (full text at CIViC)

PMID 26314551 · Ross et al., 2016 · Open in CIViC

civic