Format

Send to

Choose Destination
See comment in PubMed Commons below
Nat Med. 2015 Nov;21(11):1350-6. doi: 10.1038/nm.3967. Epub 2015 Oct 12.

The consensus molecular subtypes of colorectal cancer.

Author information

1
Sage Bionetworks, Seattle, Washington, USA.
2
Vall d'Hebron Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona, Spain.
3
Laboratory for Experimental Oncology and Radiobiology (LEXOR), Center for Experimental Molecular Medicine (CEMM), Academic Medical Center (AMC), University of Amsterdam, Amsterdam, the Netherlands.
4
Department of Biomedical Sciences, City University of Hong Kong, Hong Kong.
5
Ligue Nationale Contre le Cancer, Paris, France.
6
Netherlands Cancer Institute (NKI), Amsterdam, the Netherlands.
7
Swiss Institute of Bioinformatics (SIB), Lausanne, Switzerland.
8
Agendia NV, Amsterdam, the Netherlands.
9
Institute of Cancer Research, London, UK.
10
The University of Texas, M.D. Anderson Cancer Center, Houston, Texas, USA.
11
École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
12
Gustave Roussy, Villejuif, France.
13
Laboratorio de Genomica y Microarrays, Instituto de Investigación Sanitaria San Carlos, Hospital Clinico San Carlos, Madrid, Spain.
14
Institut Catala d'Oncologia, L'Institut d'Investigació Biomèdica de Bellvitge, Barcelona, Spain.
15
Biomedical Engineering, Oregon Health Sciences University, Portland, Oregon, USA.
16
Université Paris Descartes, Paris, France.
17
Department of Biology, Hôpital Européen Georges-Pompidou, Assistance Publique - Hôpitaux de Paris, Paris, France.
18
Ludwig Center for Cancer Research, University of Lausanne, Lausanne, Switzerland.
19
Department of Oncology, University of Lausanne, Lausanne, Switzerland.
20
Universitair ziekenhuis Leuven, Leuven, Belgium.

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-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.

PMID:
26457759
PMCID:
PMC4636487
DOI:
10.1038/nm.3967
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group Icon for PubMed Central
    Loading ...
    Support Center