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The consensus molecular subtypes of colorectal cancer.


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-? 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.

SUBMITTER: Guinney J 

PROVIDER: S-EPMC4636487 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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The consensus molecular subtypes of colorectal cancer.

Guinney Justin J   Dienstmann Rodrigo R   Wang Xin X   de Reyniès Aurélien A   Schlicker Andreas A   Soneson Charlotte C   Marisa Laetitia L   Roepman Paul P   Nyamundanda Gift G   Angelino Paolo P   Bot Brian M BM   Morris Jeffrey S JS   Simon Iris M IM   Gerster Sarah S   Fessler Evelyn E   De Sousa E Melo Felipe F   Missiaglia Edoardo E   Ramay Hena H   Barras David D   Homicsko Krisztian K   Maru Dipen D   Manyam Ganiraju C GC   Broom Bradley B   Boige Valerie V   Perez-Villamil Beatriz B   Laderas Ted T   Salazar Ramon R   Gray Joe W JW   Hanahan Douglas D   Tabernero Josep J   Bernards Rene R   Friend Stephen H SH   Laurent-Puig Pierre P   Medema Jan Paul JP   Sadanandam Anguraj A   Wessels Lodewyk L   Delorenzi Mauro M   Kopetz Scott S   Vermeulen Louis L   Tejpar Sabine S  

Nature medicine 20151012 11


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 fea  ...[more]

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