{"entity":{"id":"paper-cms-guinney-nat-med-2015","kind":"paper","name":"The consensus molecular subtypes of colorectal cancer","aka":[],"tldr":"An international consortium reconciled six competing gene-expression classifications of colorectal cancer into four consensus subtypes, from immune-active microsatellite-unstable tumours to mesenchymal tumours with the worst outlook.","summary":"Analysis of gene expression data from 4,151 colorectal cancers across 18 datasets by the Colorectal Cancer Subtyping Consortium, producing four consensus molecular subtypes: CMS1 (microsatellite instability, immune), CMS2 (canonical, WNT and MYC), CMS3 (metabolic, KRAS-enriched) and CMS4 (mesenchymal, stromal, worst survival), with about 13 percent of tumours unclassified.","asOf":"2026-09-17","links":[{"label":"Nat Med 2015","url":"https://doi.org/10.1038/nm.3967"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/26457759/"}],"tags":[],"related":["colorectal-roadmap","paper-tcga-colorectal-comprehensive-characterization-nature-2012"],"cancers":["braf-v600e-colorectal","early-onset-colorectal","colorectal"],"sections":[],"technologies":["rna-seq"],"targets":["braf","kras","mmr","tgfb1"],"drugs":[],"companies":[],"institutions":[],"pathways":["wnt","myc","tgf-beta","mismatch-repair-msi","caf-activation-desmoplasia"],"terms":["cms-subtypes","msi","sidedness"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nature-medicine"],"dependsOn":[],"notes":[],"journal":"Nature Medicine","year":2015,"doi":"10.1038/nm.3967","pmid":"26457759","authors":"Guinney J, Dienstmann R, Wang X, et al.","paperType":"translational","findings":["Four subtypes with distinct biology; CMS4 had the worst overall and relapse-free survival, CMS1 the worst survival after relapse."],"whatItMeans":"The CMS framework organises colorectal cancer biology and trial stratification; BRAF V600E tumours cluster in CMS1, and CMS4's shorter survival and stromal signalling are targets of ongoing research.","caveats":["Transcriptomic classification is not yet used to choose treatment in routine practice.","Intratumoural heterogeneity means single biopsies may misclassify."],"changedPractice":true,"participants":4151},"route":"/key-papers/paper-cms-guinney-nat-med-2015/","neighbours":{"roadmap":[{"id":"colorectal-roadmap","kind":"roadmap","name":"Colorectal cancer roadmap: from the adenoma-carcinoma sequence and the first screening trials to total mesorectal excision, oxaliplatin, RAS testing, immunotherapy for mismatch repair-deficient disease, ctDNA-guided treatment and organ preservation","route":"/roadmaps/colorectal-roadmap/"}],"paper":[{"id":"paper-tcga-colorectal-comprehensive-characterization-nature-2012","kind":"paper","name":"Comprehensive molecular characterization of human colon and rectal cancer","route":"/key-papers/paper-tcga-colorectal-comprehensive-characterization-nature-2012/"}],"cancer":[{"id":"braf-v600e-colorectal","kind":"cancer","name":"BRAF V600E-mutant colorectal cancer","route":"/cancers/braf-v600e-colorectal/"},{"id":"colorectal","kind":"cancer","name":"Colorectal cancer","route":"/cancers/colorectal/"},{"id":"early-onset-colorectal","kind":"cancer","name":"Early-onset colorectal cancer (under 50)","route":"/cancers/early-onset-colorectal/"}],"technology":[{"id":"rna-seq","kind":"technology","name":"RNA sequencing & expression profiling","route":"/technologies/rna-seq/"}],"target":[{"id":"braf","kind":"target","name":"BRAF","route":"/targets/braf/"},{"id":"kras","kind":"target","name":"KRAS","route":"/targets/kras/"},{"id":"mmr","kind":"target","name":"Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2)","route":"/targets/mmr/"},{"id":"tgfb1","kind":"target","name":"TGFB1","route":"/targets/tgfb1/"}],"pathway":[{"id":"caf-activation-desmoplasia","kind":"pathway","name":"Fibroblast activation, desmoplasia & matrix stiffness","route":"/pathways/caf-activation-desmoplasia/"},{"id":"mismatch-repair-msi","kind":"pathway","name":"Mismatch repair & microsatellite instability","route":"/pathways/mismatch-repair-msi/"},{"id":"myc","kind":"pathway","name":"MYC","route":"/pathways/myc/"},{"id":"tgf-beta","kind":"pathway","name":"TGF-β signalling","route":"/pathways/tgf-beta/"},{"id":"wnt","kind":"pathway","name":"Wnt / β-catenin","route":"/pathways/wnt/"}],"term":[{"id":"cms-subtypes","kind":"term","name":"Consensus molecular subtypes (CMS1-4)","route":"/terms/cms-subtypes/"},{"id":"msi","kind":"term","name":"Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)","route":"/terms/msi/"},{"id":"sidedness","kind":"term","name":"Sidedness (left vs right colon)","route":"/terms/sidedness/"}],"journal":[{"id":"nature-medicine","kind":"journal","name":"Nature Medicine","route":"/journals/nature-medicine/"}],"idea":[{"id":"idea-crc-mss-immunotherapy-by-biomarker-not-by-line","kind":"idea","name":"Select microsatellite stable patients for immunotherapy by a measured immune biomarker, not by how many treatments they have already failed","route":"/ideas/idea-crc-mss-immunotherapy-by-biomarker-not-by-line/"}]}}