# BRAF V600E (and V600K)

Source: https://onco.cc/biomarkers/braf-v600e/  
OnCo record `braf-v600e` (Biomarker). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

V600E is the BRAF change that drives half of melanomas and many thyroid, bowel, lung and brain tumours. BRAF plus MEK inhibitors are approved for it in melanoma, lung, thyroid and, tumour-agnostically, any solid tumour; in bowel cancer it is treated with encorafenib and cetuximab.

## Summary

The c.1799T>A (V600E) substitution, and the rarer V600K, are class I BRAF mutations that signal as monomers and respond to BRAF inhibitors. Dabrafenib and vemurafenib are labelled for BRAF V600E melanoma; dabrafenib with trametinib for V600E or V600K melanoma, V600E NSCLC, anaplastic thyroid cancer, paediatric low-grade glioma and V600E solid tumours (tumour-agnostic, 2022); encorafenib with binimetinib for V600E or V600K melanoma and V600E NSCLC, and with cetuximab for V600E colorectal cancer. Companion diagnostics on the FDA list include the cobas 4800 BRAF V600, THxID BRAF, therascreen BRAF V600E, FoundationOne CDx and Liquid CDx, Oncomine Dx Target Test, Guardant360 CDx and Caris MI Cancer Seek. Labels warn the drugs are not for BRAF wild-type tumours.

## Fields

- Kind: Biomarker
- Last checked: 2026-09-23
- Also known as: BRAF V600E; V600E; BRAF V600; BRAF V600K; BRAF-mutant; BRAF class I mutation; BRAF V600E-mutant
- Tags: biomarker; braf

## Notes

- Colorectal cancer: V600E in 6 to 18% by cohort and 8.2% of first-line metastatic patients; the threshold is simply the presence of the allele. It does three jobs here. It is prognostic (overall survival hazard ratio 1.91, and the shorter survival of mismatch repair deficiency is itself driven by co-occurring BRAF mutation; Venderbosch 2014). It is predictive, selecting encorafenib plus cetuximab, now first line with chemotherapy (BEACON CRC, BREAKWATER). And it is a reflex test in MLH1-deficient tumours, because BRAF V600E points to sporadic CIMP-associated methylation rather than Lynch syndrome (Weisenberger 2006). Non-V600 BRAF mutations, 22% of all BRAF mutations found, do not qualify for the regimen and carry a far better prognosis (Jones 2017).
- Gallbladder cancer: BRAF mutation in 7 of 244 samples (2.9%) in cBioPortal gbc_mskcc_2022; the tumour-agnostic dabrafenib plus trametinib indication applies to V600E.
- Lung cancer: 1 to 2% of adenocarcinomas, and, unlike in melanoma, a minority of all BRAF mutations found: 31 of 133 BRAF mutation records in the largest panel cohort and 9 of 45 in the TCGA adenocarcinomas (cBioPortal). A BRAF-mutant lung cancer therefore has to be read allele by allele before the licensed combination is considered.

## Sources

- Tafinlar prescribing information (DailyMed): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fee1e6b1-e1a5-4254-9f2e-a70e0f8dbdea
- BRAFTOVI prescribing information (DailyMed): https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=235dfc38-0f0b-4037-b501-7a9f4294740c

## Connected records

- biomarkers: [BRAF class II and class III mutations (non-V600)](https://onco.cc/biomarkers/braf-class-ii-iii/), [BRAF fusion or rearrangement](https://onco.cc/biomarkers/braf-fusion/), [KRAS G12C](https://onco.cc/biomarkers/kras-g12c/), [RAS wild-type (extended KRAS and NRAS testing)](https://onco.cc/biomarkers/ras-wild-type/)
- cancers: [Advanced melanoma (unresectable stage III and stage IV)](https://onco.cc/cancers/advanced-melanoma/), [Anaplastic thyroid cancer](https://onco.cc/cancers/anaplastic-thyroid-cancer/), [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Gallbladder cancer](https://onco.cc/cancers/gallbladder/), [Melanoma](https://onco.cc/cancers/melanoma/), [Metastatic cancer (cancer that has spread)](https://onco.cc/cancers/metastatic-cancer/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [Paediatric low-grade glioma](https://onco.cc/cancers/paediatric-low-grade-glioma/), [Thyroid cancer](https://onco.cc/cancers/thyroid/)
- drugs: [Binimetinib](https://onco.cc/drugs/binimetinib/), [Cetuximab](https://onco.cc/drugs/cetuximab/), [Cobimetinib](https://onco.cc/drugs/cobimetinib/), [Dabrafenib](https://onco.cc/drugs/dabrafenib/), [Dabrafenib + trametinib](https://onco.cc/drugs/dabrafenib-trametinib/), [Encorafenib](https://onco.cc/drugs/encorafenib/), [therascreen companion diagnostic kits (KRAS, EGFR, PIK3CA, FGFR, BRAF)](https://onco.cc/drugs/therascreen-cdx/), [Trametinib](https://onco.cc/drugs/trametinib/), [Vemurafenib](https://onco.cc/drugs/vemurafenib/)
- terms: [BRAF V600E mutation](https://onco.cc/terms/braf-v600-mutation/), [Next-generation sequencing (NGS)](https://onco.cc/terms/ngs/), [Tumour-agnostic (tissue-agnostic) approval](https://onco.cc/terms/tumour-agnostic/)
- key papers: [BREAKWATER: encorafenib plus cetuximab with chemotherapy as first treatment for BRAF V600E-mutated colorectal cancer](https://onco.cc/key-papers/paper-breakwater-nejm-2025/), [Comprehensive molecular characterization of gallbladder carcinoma and potential targets for intervention](https://onco.cc/key-papers/paper-giraldo-gallbladder-msk-impact-ccr-2022/), [CpG island methylator phenotype underlies sporadic microsatellite instability and is tightly associated with BRAF mutation in colorectal cancer](https://onco.cc/key-papers/paper-weisenberger-cimp-braf-mlh1-colorectal-nat-genet-2006/), [Encorafenib, binimetinib, and cetuximab in BRAF V600E-mutated colorectal cancer (BEACON CRC)](https://onco.cc/key-papers/paper-kopetz-beacon-encorafenib-braf-colorectal-nejm-2019/), [Mismatch repair status and BRAF mutation status in metastatic colorectal cancer: a pooled analysis of the CAIRO, CAIRO2, COIN and FOCUS studies](https://onco.cc/key-papers/paper-venderbosch-mmr-braf-metastatic-colorectal-pooled-ccr-2014/), [Non-V600 BRAF mutations define a clinically distinct molecular subtype of metastatic colorectal cancer](https://onco.cc/key-papers/paper-jones-non-v600-braf-colorectal-jco-2017/), [Using multiplexed assays of oncogenic drivers in lung cancers to select targeted drugs](https://onco.cc/key-papers/paper-kris-lung-cancer-mutation-consortium-jama-2014/)
- targets: [BRAF](https://onco.cc/targets/braf/)

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