%0 Journal Article
%T The consensus molecular subtypes of colorectal cancer.
%A Guinney J
%A Dienstmann R
%A Wang X
%A de Reyniès A
%A Schlicker A
%A Soneson C
%A Marisa L
%A Roepman P
%A Nyamundanda G
%A Angelino P
%A Bot BM
%A Morris JS
%A Simon IM
%A Gerster S
%A Fessler E
%A De Sousa E Melo F
%A Missiaglia E
%A Ramay H
%A Barras D
%A Homicsko K
%A Maru D
%A Manyam GC
%A Broom B
%A Boige V
%A Perez-Villamil B
%A Laderas T
%A Salazar R
%A Gray JW
%A Hanahan D
%A Tabernero J
%A Bernards R
%A Friend SH
%A Laurent-Puig P
%A Medema JP
%A Sadanandam A
%A Wessels L
%A Delorenzi M
%A Kopetz S
%A Vermeulen L
%A Tejpar S
%J Nat Med
%V 21
%N 11
%D Nov 2015
%M 26457759
%F 87.241
%R 10.1038/nm.3967
%X 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.