The consensus molecular subtypes of colorectal cancer

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 shar...

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Published inNature medicine
Main Authors Guinney, Justin, Dienstmann, Rodrigo, Wang, Xin, Reyniès, Aurélien de, Schlicker, Andreas, Soneson, Charlotte, Marisa, Laetitia, Roepman, Paul, Nyamundanda, Gift, Angelino, Paolo, Bot, Brian M, Morris,Jeffrey, Simon, Iris M, Gerster, Sarah, Fessler, Evelyn, Sousa e Melo, Felipe de, Missiaglia, Edoardo, Ramay, Hena, Barras, David, Homicsko, Krisztian, Maru, Dipen, Manyam, Ganiraju C, Broom, Bradley, Boige, Valerie, Perez Villamil,Beatriz, Laderas, Ted, Salazar Soler, Ramón, Gray, Joe W, Hanahan, Douglas, Tabernero, Josep, Bernards, Rene, Friend, Stephen H, Laurent Puig, Pierre, Medema, Jan Paul, Sadanandam, Anguraj, Wessels, Lodewyk, Delorenzi, Mauro, Kopetz, Scott, Vermeulen, Louis, Tejpar, Sabine
Format Journal Article
LanguageEnglish
Published Nature Publishing Group 01.11.2015
Subjects
Classificació de tumors
Colorectal cancer
Càncer colorectal
Oncologia
Oncology
Tumors classification
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Summary: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-beta 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.
ISSN:1078-8956