The consensus molecular subtypes of colorectal cancer
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.
Overview
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.
- Four subtypes with distinct biology; CMS4 had the worst overall and relapse-free survival, CMS1 the worst survival after relapse.
The CMS framework organises colorectal cancer biology and trial stratification; BRAF V600E tumours cluster in CMS1, and CMS4's poor prognosis and stromal signalling are targets of ongoing research.
- Transcriptomic classification is not yet used to choose treatment in routine practice.
- Intratumoural heterogeneity means single biopsies may misclassify.