{"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 one uniform outlook, 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/"}]}}