The Consensus Molecular Subtypes of Colorectal Cancer
Guinney, Justin (Fred Hutchinson Cancer Research Center)
Dienstmann, Rodrigo (Vall d'Hebron Institut d'Oncologia)
Wang, Xin (City University of Hong Kong. Department of Biomedical Sciences (China))
de Reyniès, Aurélien (Ligue Nationale Contre le Cancer (France))
Schlicker, Andreas (The Netherlands Cancer Institute (Amsterdam, Països Baixos))
Soneson, Charlotte (SIB Swiss Institute of Bioinformatics (Switzerland))
Marisa, Laetitia (Ligue Nationale Contre le Cancer (France))
Roepman, Paul (Agendia NV (Netherlands))
Nyamundanda, Gift (The Institute of Cancer Research (UK))
Angelino, Paolo (SIB Swiss Institute of Bioinformatics (Switzerland))
Bot, Brian M. (Fred Hutchinson Cancer Research Center)
Morris, Jeffrey S. (The University of Texas M.D. Anderson Cancer Center (USA))
Simon, Iris M. (Agendia NV (Netherlands))
Gerster, Sarah (SIB Swiss Institute of Bioinformatics (Switzerland))
Fessler, Evelyn (University of Amsterdam (Netherlands))
de Sousa e Melo, Felipe (University of Amsterdam (Netherlands))
Missiaglia, Edoardo (SIB Swiss Institute of Bioinformatics (Switzerland))
Ramay, Hena (SIB Swiss Institute of Bioinformatics (Switzerland))
Barras, David (SIB Swiss Institute of Bioinformatics (Switzerland))
Homicsko, Krisztian (Ecole Polytechnique Federale de Lausanne (Switzerland))
Maru, Dipen (The University of Texas M.D. Anderson Cancer Center, Houston (USA))
Manyam, Ganiraju C. (The University of Texas M.D. Anderson Cancer Center, Houston (USA))
Broom, Bradley (The University of Texas M.D. Anderson Cancer Center, Houston (USA))
Boige, Valerie (Gustave Roussy, Villejuif (France))
Perez-Villamil, Beatriz (Instituto de Investigación Sanitaria del Hospital Clínico San Carlos)
Laderas, Ted (Fred Hutchinson Cancer Research Center)
Salazar, Ramon (Institut d'Investigació Biomèdica de Bellvitge)
Gray, Joe W. (Oregon Health Sciences University (USA))
Hanahan, Douglas (Ecole Polytechnique Federale de Lausanne (Switzerland))
Tabernero, Josep (Vall d'Hebron Institut d'Oncologia)
Bernards, Rene (The Netherlands Cancer Institute (Amsterdam, Països Baixos))
Friend, Stephen H. (Fred Hutchinson Cancer Research Center)
Laurent-Puig, Pierre (Universite Paris Descartes (France))
Medema, Jan Paul (LEXOR, Center for Experimental Molecular Medicine (CEMM), Academic Medical Center (AMC), University of Amsterdam (Netherlands))
Sadanandam, Anguraj (The Institute of Cancer Research (UK))
Wessels, Lodewyk (The Netherlands Cancer Institute (Amsterdam, Països Baixos))
Delorenzi, Mauro (University of Lausanne (Switzerland))
Kopetz, Scott (The University of Texas M.D. Anderson Cancer Center (USA))
Vermeulen, Louis (LEXOR, Center for Experimental Molecular Medicine (CEMM), Academic Medical Center (AMC), University of Amsterdam (Netherlands))
Tejpar, Sabine (Universitair ziekenhuis Leuven (Belgium))
Universitat Autònoma de Barcelona

Fecha:	2015
Resumen:	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 (CMS) with distinguishing features: CMS1 (MSI Immune, 14%), hypermutated, microsatellite unstable, strong immune activation; CMS2 (Canonical, 37%), epithelial, chromosomally unstable, marked WNT and MYC signaling activation; CMS3 (Metabolic, 13%), epithelial, 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 intra-tumoral 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.
Ayudas:	European Commission 638193
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Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Publicado en:	Nature Medicine, Vol. 21, Num. 11 (November 2015) , p. 1350-1356, ISSN 1546-170X

DOI: 10.1038/nm.3967
PMID: 26457759

33 p, 1.9 MB

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