The consensus molecular subtypes of colorectal cancer

Justin Guinney, Rodrigo Dienstmann, Xin Wang, Aurélien De Reyniès, Andreas Schlicker, Charlotte Soneson, Laetitia Marisa, Paul Roepman, Gift Nyamundanda, Paolo Angelino, Brian M. Bot, Jeffrey S. Morris, Iris M. Simon, Sarah Gerster, Evelyn Fessler, Felipe De Sousa .E Melo, Edoardo Missiaglia, Hena Ramay, David Barras, Krisztian HomicskoDipen Maru, Ganiraju C. Manyam, Bradley Broom, Valerie Boige, Beatriz Perez-Villamil, Ted Laderas, Ramon Salazar, Joe W. Gray, Douglas Hanahan, Josep Tabernero, Rene Bernards, Stephen H. Friend, Pierre Laurent-Puig, Jan Paul Medema, Anguraj Sadanandam, Lodewyk Wessels, Mauro Delorenzi, Scott Kopetz, Louis Vermeulen, Sabine Tejpar

Research output: Contribution to journalArticle

1408 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1350-1356
Number of pages7
JournalNature medicine
Volume21
Issue number11
DOIs
StatePublished - Nov 1 2015

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Guinney, J., Dienstmann, R., Wang, X., De Reyniès, A., Schlicker, A., Soneson, C., Marisa, L., Roepman, P., Nyamundanda, G., Angelino, P., Bot, B. M., Morris, J. S., Simon, I. M., Gerster, S., Fessler, E., De Sousa .E Melo, F., Missiaglia, E., Ramay, H., Barras, D., ... Tejpar, S. (2015). The consensus molecular subtypes of colorectal cancer. Nature medicine, 21(11), 1350-1356. https://doi.org/10.1038/nm.3967