# The consensus molecular subtypes of colorectal cancer

Source: https://onco.cc/key-papers/paper-cms-guinney-nat-med-2015/  
OnCo record `paper-cms-guinney-nat-med-2015` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Key paper
- Last checked: 2026-09-17
- Journal: Nature Medicine
- Year: 2015
- DOI: 10.1038/nm.3967
- Authors: Guinney J, Dienstmann R, Wang X, et al.
- Findings: Four subtypes with distinct biology; CMS4 had the worst overall and relapse-free survival, CMS1 the worst survival after relapse.
- What it means: 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.

## Sources

- Nat Med 2015: https://doi.org/10.1038/nm.3967
- PubMed: https://pubmed.ncbi.nlm.nih.gov/26457759/

## Connected records

- roadmaps: [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](https://onco.cc/roadmaps/colorectal-roadmap/)
- key papers: [Comprehensive molecular characterization of human colon and rectal cancer](https://onco.cc/key-papers/paper-tcga-colorectal-comprehensive-characterization-nature-2012/)
- cancers: [BRAF V600E-mutant colorectal cancer](https://onco.cc/cancers/braf-v600e-colorectal/), [Colorectal cancer](https://onco.cc/cancers/colorectal/), [Early-onset colorectal cancer (under 50)](https://onco.cc/cancers/early-onset-colorectal/)
- technologies: [RNA sequencing & expression profiling](https://onco.cc/technologies/rna-seq/)
- targets: [BRAF](https://onco.cc/targets/braf/), [KRAS](https://onco.cc/targets/kras/), [Mismatch repair proteins (MLH1, MSH2, MSH6, PMS2)](https://onco.cc/targets/mmr/), [TGFB1](https://onco.cc/targets/tgfb1/)
- pathways: [Fibroblast activation, desmoplasia & matrix stiffness](https://onco.cc/pathways/caf-activation-desmoplasia/), [Mismatch repair & microsatellite instability](https://onco.cc/pathways/mismatch-repair-msi/), [MYC](https://onco.cc/pathways/myc/), [TGF-β signalling](https://onco.cc/pathways/tgf-beta/), [Wnt / β-catenin](https://onco.cc/pathways/wnt/)
- terms: [Consensus molecular subtypes (CMS1-4)](https://onco.cc/terms/cms-subtypes/), [Microsatellite instability (MSI-H) / mismatch repair deficiency (dMMR)](https://onco.cc/terms/msi/), [Sidedness (left vs right colon)](https://onco.cc/terms/sidedness/)
- journals: [Nature Medicine](https://onco.cc/journals/nature-medicine/)
- ideas: [Select microsatellite stable patients for immunotherapy by a measured immune biomarker, not by how many treatments they have already failed](https://onco.cc/ideas/idea-crc-mss-immunotherapy-by-biomarker-not-by-line/)

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