# Non-V600 BRAF mutations define a clinically distinct molecular subtype of metastatic colorectal cancer

Source: https://onco.cc/key-papers/paper-jones-non-v600-braf-colorectal-jco-2017/  
OnCo record `paper-jones-non-v600-braf-colorectal-jco-2017` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Not every BRAF mutation is the notorious one. The other 22% of BRAF-mutant bowel cancers occur in younger patients, on the left, and live five times longer than the V600E group.

## Summary

A multicentre retrospective cohort study pooled patients with non-V600 BRAF mutations from next-generation sequencing databases at three large molecular genetics reference laboratories. Of 9,643 patients with metastatic colorectal cancer tested, 208 had non-V600 BRAF mutations, 2.2% of all patients and 22% of all BRAF mutations identified. Compared with V600E BRAF-mutant cancers, non-V600 cancers occurred in significantly younger patients (58 against 68 years), fewer female patients (46% against 65%), fewer high-grade tumours (13% against 64%) and fewer right-sided primaries (36% against 81%). Median overall survival was 60.7 months for non-V600 BRAF against 11.4 months for V600E and 43.0 months for BRAF wild-type disease, and in multivariable analysis non-V600 BRAF mutation was independently associated with improved overall survival (hazard ratio 0.18).

## Fields

- Kind: Key paper
- Last checked: 2026-09-24
- Journal: Journal of Clinical Oncology
- Year: 2017
- DOI: 10.1200/JCO.2016.71.4394
- Authors: Jones JC, Renfro LA, Al-Shamsi HO, et al.
- Findings: Non-V600 BRAF mutations in 208 of 9,643 patients (2.2%), 22% of all BRAF mutations.; Median overall survival 60.7 months against 11.4 for V600E and 43.0 for BRAF wild-type.; Younger, more often left-sided and lower grade than V600E.
- What it means: It stops a BRAF-mutant report being read as a death sentence, and it separates the class II and III mutations, which signal differently and are not covered by the encorafenib plus cetuximab label, from V600E.
- Caveats: Retrospective across three commercial sequencing databases, so ascertainment and follow-up are uneven.; Non-V600 is a heterogeneous group of class II and class III alleles with different biology.; No approved therapy follows from a non-V600 BRAF result.

## Sources

- Jones et al., J Clin Oncol 2017: non-V600 BRAF mutations in 9,643 sequenced metastatic colorectal cancers: https://doi.org/10.1200/JCO.2016.71.4394
- PubMed: https://pubmed.ncbi.nlm.nih.gov/28486044/

## Connected records

- cancers: [Colorectal cancer](https://onco.cc/cancers/colorectal/)
- targets: [BRAF](https://onco.cc/targets/braf/)
- institutions: [Mayo Clinic](https://onco.cc/institutions/mayo-clinic/), [MD Anderson Cancer Center](https://onco.cc/institutions/md-anderson/)
- pathways: [RAS / RAF / MEK / ERK (MAPK)](https://onco.cc/pathways/ras-mapk/)
- terms: [Next-generation sequencing (NGS)](https://onco.cc/terms/ngs/), [Sidedness (left vs right colon)](https://onco.cc/terms/sidedness/)
- people: [Scott Kopetz](https://onco.cc/people/scott-kopetz/)
- journals: [Journal of Clinical Oncology](https://onco.cc/journals/jco/)
- trials: [BEACON CRC](https://onco.cc/trials/beacon-crc/), [BREAKWATER](https://onco.cc/trials/breakwater/)
- drugs: [Encorafenib](https://onco.cc/drugs/encorafenib/)
- biomarkers: [BRAF class II and class III mutations (non-V600)](https://onco.cc/biomarkers/braf-class-ii-iii/), [BRAF V600E (and V600K)](https://onco.cc/biomarkers/braf-v600e/)

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