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The consensus molecular subtypes of colorectal cancer

2015; Nature Portfolio; Volume: 21; Issue: 11 Linguagem: Inglês

10.1038/nm.3967

1546-170X

Justin Guinney, Rodrigo Dienstmann, Xin Wang, Aurélien de Reyniès, Andreas Schlicker, Charlotte Soneson, Laëtitia Marisa, Paul Roepman, Gift Nyamundanda, Paolo Angelino, Brian M. Bot, Jeffrey S. Morris, Iris Simón, Sarah Gerster, Evelyn Fessler, Felipe de Sousa e Melo, Edoardo Missiaglia, Hena R. Ramay, David Barras, Krisztián Homicskó, Dipen Maru, Ganiraju C. Manyam, Bradley M. Broom, Valérie Boige, Beatriz Pérez‐Villamil, Ted Laderas, Ramón Salazar, Joe W. Gray, Douglas Hanahan, Josep Tabernero, René Bernards, Stephen Friend, Pierre Laurent‐Puig, Jan Paul Medema, Anguraj Sadanandam, Lodewyk F.A. Wessels, Mauro Delorenzi, Scott Kopetz, Louis Vermeulen, Sabine Tejpar,

Ferroptosis and cancer prognosis

An international consortium of colorectal cancer researchers undertakes a large-scale data sharing project to achieve a consensus molecular classification of colorectal cancers. 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.