期刊
NATURE MEDICINE
卷 21, 期 11, 页码 1350-1356出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/nm.3967
关键词
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资金
- National Cancer Institute [U54CA149237]
- La Caixa International Program for Cancer Research Education
- Dutch Cancer Society [UVA2011-4969, UVA2014-7245, UVA2012-573, UVA2013-6331, UVA2015-7587]
- Worldwide Cancer Research [14-1164]
- Maag Lever Darm Stichting (MLDS) [MLDS-CDG 14-03]
- European Research Council [ERG-StG 638193]
- MLDS [FP012]
- US National Institutes of Health [R01CA172670, R01CA184843, R01 CA187238, P30CA016672]
- National Health Service
- Katholieke Universiteit Leuven [GOA/12/2106]
- EU
- Research Foundation Flanders
- Belgian National Cancer Plan
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.
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