The consensus molecular subtypes of colorectal cancer

被引：3915

作者：

Guinney, Justin ^{[1
]}

Dienstmann, Rodrigo ^{[1
,2
]}

Wang, Xin ^{[3
,4
]}

de Reynies, Aurelien ^{[5
]}

Schlicker, Andreas ^{[6
]}

Soneson, Charlotte ^{[7
]}

Marisa, Laetitia ^{[5
]}

Roepman, Paul ^{[8
]}

Nyamundanda, Gift ^{[9
]}

Angelino, Paolo ^{[7
]}

Bot, Brian M. ^{[1
]}

Morris, Jeffrey S. ^{[10
]}

Simon, Iris M. ^{[8
]}

Gerster, Sarah ^{[7
]}

Fessler, Evelyn ^{[3
]}

Melo, Felipe De Sousa E. ^{[3
]}

Missiaglia, Edoardo ^{[7
]}

Ramay, Hena ^{[7
]}

Barras, David ^{[7
]}

Homicsko, Krisztian ^{[11
]}

Maru, Dipen ^{[10
]}

Manyam, Ganiraju C. ^{[10
]}

Broom, Bradley ^{[10
]}

Boige, Valerie ^{[12
]}

Perez-Villamil, Beatriz ^{[13
]}

Laderas, Ted ^{[1
]}

Salazar, Ramon ^{[14
]}

Gray, Joe W. ^{[15
]}

Hanahan, Douglas ^{[11
]}

Tabernero, Josep ^{[2
]}

Bernards, Rene ^{[6
]}

Friend, Stephen H. ^{[1
]}

Laurent-Puig, Pierre ^{[16
,17
]}

Medema, Jan Paul ^{[3
]}

Sadanandam, Anguraj ^{[9
]}

Wessels, Lodewyk ^{[6
]}

Delorenzi, Mauro ^{[7
,18
,19
]}

Kopetz, Scott ^{[10
]}

Vermeulen, Louis ^{[3
]}

Tejpar, Sabine ^{[20
]}

机构：

[1] Sage Bionetworks, Seattle, WA 98109 USA

[2] Univ Autonoma Barcelona, Vall dHebron Inst Oncol, E-08193 Barcelona, Spain

[3] Univ Amsterdam, Acad Med Ctr, Lab Expt Oncol & Radiobiol LEXOR, Ctr Expt Mol Med, NL-1105 AZ Amsterdam, Netherlands

[4] City Univ Hong Kong, Dept Biomed Sci, Hong Kong, Hong Kong, Peoples R China

[5] Ligue Natl Canc, Paris, France

[6] Netherlands Canc Inst NKI, Amsterdam, Netherlands

[7] Swiss Inst Bioinformat, Lausanne, Switzerland

[8] Agendia NV, Amsterdam, Netherlands

[9] Inst Canc Res, London SW3 6JB, England

[10] Univ Texas MD Anderson Canc Ctr, Houston, TX 77030 USA

[11] Ecole Polytech Fed Lausanne, Lausanne, Switzerland

[12] Gustave Roussy, Villejuif, France

[13] Hosp Clin San Carlos, Inst Invest Sanitaria San Carlos, Lab Genom & Microarrays, Madrid, Spain

[14] Inst Invest Biomed Bellvitge, Inst Catala Oncol, Barcelona, Spain

[15] Oregon Hlth & Sci Univ, Biomed Engn, Portland, OR USA

[16] Univ Paris 05, Paris, France

[17] Hop Europeen Georges Pompidou, AP HP, Dept Biol, Paris, France

[18] Univ Lausanne, Ludwig Ctr Canc Res, Lausanne, Switzerland

[19] Univ Lausanne, Dept Oncol, Lausanne, Switzerland

[20] Univ Ziekenhuis Leuven, Leuven, Belgium

来源：

NATURE MEDICINE | 2015年 / 21卷 / 11期

基金：

美国国家卫生研究院; 欧洲研究理事会;

关键词：

III COLON-CANCER; MICROSATELLITE INSTABILITY; TUMORS; CLASSIFICATION; PHENOTYPE; RESPONSES; MUTATION; GROWTH; CELLS; BRAF;

D O I：

10.1038/nm.3967

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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.

引用

页码：1350 / 1356

页数：7

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