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The consensus molecular subtypes of colorectal cancer

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

in 38/39 / 38/61 / 631/67/1504/1885 / 631/67/69 / analysis / Biomedicine / Cancer Research / Carcinoma - classification / Carcinoma - genetics / Carcinoma - pathology / Care and treatment / Classificació de tumors / Classification / Colorectal cancer / Colorectal carcinoma / Colorectal Neoplasms - classification / Colorectal Neoplasms - genetics / Colorectal Neoplasms - pathology / Consensus / CpG Islands / Càncer colorectal / DNA Copy Number Variations - genetics / DNA Methylation / Gene expression / Gene Expression Profiling / Gene Expression Regulation, Neoplastic / Genes, myc - genetics / Genomics / Genotype & phenotype / Heterogeneity / Humans / Infectious Diseases / Information Dissemination / Liquid chromatography / Metabolic Diseases / MicroRNA / Microsatellite Instability / Molecular Medicine / Mutation - genetics / Neovascularization, Pathologic - genetics / Neovascularization, Pathologic - pathology / Neurosciences / Oncologia / Oncology / Phenotype / Proto-Oncogene Proteins - genetics / Proto-Oncogene Proteins B-raf - genetics / Proto-Oncogene Proteins p21(ras) / ras Proteins - genetics / Transforming Growth Factor beta - genetics / Transforming growth factors / Tumors classification / Wnt Signaling Pathway - genetics

2015

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2015

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Journal Article

The consensus molecular subtypes of colorectal cancer

Delorenzi, Mauro,

Fessler, Evelyn,

Sadanandam, Anguraj,

Wang, Xin,

Morris, Jeffrey S,

Tabernero, Josep,

Perez-Villamil, Beatriz,

Maru, Dipen,

Roepman, Paul,

Simon, Iris M,

Nyamundanda, Gift,

Boige, Valerie,

Medema, Jan Paul,

Kopetz, Scott,

Marisa, Laetitia,

Wessels, Lodewyk,

Dienstmann, Rodrigo,

Laderas, Ted,

Homicsko, Krisztian,

Missiaglia, Edoardo,

Vermeulen, Louis,

Bot, Brian M,

Laurent-Puig, Pierre,

Ramay, Hena,

Tejpar, Sabine,

De Sousa E Melo, Felipe,

Manyam, Ganiraju C,

de Reyniès, Aurélien,

Friend, Stephen H,

Broom, Bradley,

Gray, Joe W,

Angelino, Paolo,

Gerster, Sarah,

Bernards, Rene,

Schlicker, Andreas,

Salazar, Ramon,

Soneson, Charlotte,

Hanahan, Douglas,

Guinney, Justin,

Barras, David

2015

Overview

An international consortium of colorectal cancer researchers undertakes a large-scale data sharing project to achieve a consensus molecular classification of colorectal cancers. 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.

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Nature Publishing Group US,Nature Publishing Group

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