The consensus molecular subtypes of colorectal cancer

An international consortium of 7 research teams, including the CIT team, just published in Nature Medicine [1] a  consensus classification of colorectal cancers (CRC) based on gene expression data.

Based on the analysis of more than 4,000 tumor samples, this work lead to a consensus on the existence of  4 molecular subtypes of colorectal cancers, thoroughly characterized at the molecular and clinical level :

  • The ‘MSI immune’ type (14% of cases) : hypermutated tumors, with a majority bearing microsatellite instability (MSI) and a prominent immune infiltration,
  • The Canonical type (37% of cases) : tumors with chromosomal instability and mutations in the APC and TP53 genes, illustrating the canonical carcinogenesis described by Fearon and Vogelstein in 1990,
  • The Metabolic type (13% of cases) : chiefly mutated in the KRAS oncogene and overexpress metabolic pathways,
  • The Mesenchymal type (23% of cases), associated to a bad prognosis : highly infiltrated tumors that overexpress genes of the Epithelial-Mesenchymal transition.

It is the first international collaboration that successfully lead to the molecular classification of a cancer. The classification into 4 molecular subgroups can hereon be used as a standard by the scientific community, in particular for the identification of targeted therapy and for the stratification of clinical trials.

ConsensusCRCCS_NatMed2015

[1] Guinney, J., Dienstmann, R., Wang, X., de Reyniès, A., Schlicker, A., Soneson, C., Marisa, L., Roepman, P., Nyamundanda, G., Angelino, P., et al. (2015). The consensus molecular subtypes of colorectal cancer. Nature Medicine advance online publication.