{"entity":{"id":"paper-jones-non-v600-braf-colorectal-jco-2017","kind":"paper","name":"Non-V600 BRAF mutations define a clinically distinct molecular subtype of metastatic colorectal cancer","aka":[],"tldr":"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).","asOf":"2026-09-24","links":[{"label":"Jones et al., J Clin Oncol 2017: non-V600 BRAF mutations in 9,643 sequenced metastatic colorectal cancers","url":"https://doi.org/10.1200/JCO.2016.71.4394"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/28486044/"}],"tags":[],"related":[],"cancers":["colorectal"],"sections":[],"technologies":[],"targets":["braf"],"drugs":[],"companies":[],"institutions":["mayo-clinic","md-anderson"],"pathways":["ras-mapk"],"terms":["sidedness","ngs"],"trials":[],"people":["scott-kopetz"],"bottlenecks":[],"keyPapers":[],"journals":["jco"],"dependsOn":[],"notes":[],"journal":"Journal of Clinical Oncology","year":2017,"doi":"10.1200/JCO.2016.71.4394","pmid":"28486044","authors":"Jones JC, Renfro LA, Al-Shamsi HO, et al.","paperType":"observational","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."],"whatItMeans":"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."],"changedPractice":false,"participants":9643},"route":"/key-papers/paper-jones-non-v600-braf-colorectal-jco-2017/","neighbours":{"cancer":[{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"}],"target":[{"id":"braf","kind":"target","name":"BRAF","route":"/targets/braf/"}],"institution":[{"id":"mayo-clinic","kind":"institution","name":"Mayo Clinic","route":"/institutions/mayo-clinic/"},{"id":"md-anderson","kind":"institution","name":"MD Anderson Cancer Center","route":"/institutions/md-anderson/"}],"pathway":[{"id":"ras-mapk","kind":"pathway","name":"RAS / RAF / MEK / ERK (MAPK)","route":"/pathways/ras-mapk/"}],"term":[{"id":"ngs","kind":"term","name":"Next-generation sequencing (NGS)","route":"/terms/ngs/"},{"id":"sidedness","kind":"term","name":"Sidedness (left vs right colon)","route":"/terms/sidedness/"}],"person":[{"id":"scott-kopetz","kind":"person","name":"Scott Kopetz","route":"/people/scott-kopetz/"}],"journal":[{"id":"jco","kind":"journal","name":"Journal of Clinical Oncology","route":"/journals/jco/"}],"trial":[{"id":"beacon-crc","kind":"trial","name":"BEACON CRC","route":"/trials/beacon-crc/"},{"id":"breakwater","kind":"trial","name":"BREAKWATER","route":"/trials/breakwater/"}],"drug":[{"id":"encorafenib","kind":"drug","name":"Encorafenib","route":"/drugs/encorafenib/"}],"biomarker":[{"id":"braf-class-ii-iii","kind":"biomarker","name":"BRAF class II and class III mutations (non-V600)","route":"/biomarkers/braf-class-ii-iii/"},{"id":"braf-v600e","kind":"biomarker","name":"BRAF V600E (and V600K)","route":"/biomarkers/braf-v600e/"}]}}