The consensus molecular subtypes of colorectal cancer

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Abstract

Colorectal cancer (CRC) is a frequently lethal disease with heterogeneous outcomes and drug responses. To resolve inconsistencies among the reported gene expression-based CRC classifications and facilitate clinical translation, we formed an international consortium dedicated to large-scale data sharing and analytics across expert groups. We show marked interconnectivity between six independent classification systems coalescing into four consensus molecular subtypes (CMSs) with distinguishing features: CMS1 (microsatellite instability immune, 14%), hypermutated, microsatellite unstable and strong immune activation; CMS2 (canonical, 37%), epithelial, marked WNT and MYC signaling activation; CMS3 (metabolic, 13%), epithelial and evident metabolic dysregulation; and CMS4 (mesenchymal, 23%), prominent transforming growth factor-β activation, stromal invasion and angiogenesis. Samples with mixed features (13%) possibly represent a transition phenotype or intratumoral heterogeneity. We consider the CMS groups the most robust classification system currently available for CRC - with clear biological interpretability - and the basis for future clinical stratification and subtype-based targeted interventions.

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Guinney, J., Dienstmann, R., Wang, X., De Reyniès, A., Schlicker, A., Soneson, C., … Tejpar, S. (2015). The consensus molecular subtypes of colorectal cancer. Nature Medicine, 21(11), 1350–1356. https://doi.org/10.1038/nm.3967

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