The consensus molecular subtypes of colorectal cancer

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

doi:10.1038/nm.3967

The consensus molecular subtypes of colorectal cancer

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

Center for Spatial Systems Biomedicine

Research output: Contribution to journal › Article › peer-review

3244 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1350-1356
Number of pages	7
Journal	Nature medicine
Volume	21
Issue number	11
DOIs	https://doi.org/10.1038/nm.3967
State	Published - Nov 1 2015

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1038/nm.3967

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Guinney, J., Dienstmann, R., Wang, X., De Reyniès, A., Schlicker, A., Soneson, C., Marisa, L., Roepman, P., Nyamundanda, G., Angelino, P., Bot, B. M., Morris, J. S., Simon, I. M., Gerster, S., Fessler, E., De Sousa .E Melo, F., Missiaglia, E., Ramay, H., Barras, D., ... Tejpar, S. (2015). The consensus molecular subtypes of colorectal cancer. Nature medicine, 21(11), 1350-1356. https://doi.org/10.1038/nm.3967

Guinney, J, Dienstmann, R, Wang, X, De Reyniès, A, Schlicker, A, Soneson, C, Marisa, L, Roepman, P, Nyamundanda, G, Angelino, P, Bot, BM, Morris, JS, Simon, IM, Gerster, S, Fessler, E, De Sousa .E Melo, F, Missiaglia, E, Ramay, H, Barras, D, Homicsko, K, Maru, D, Manyam, GC, Broom, B, Boige, V, Perez-Villamil, B, Laderas, T, Salazar, R, Gray, JW, Hanahan, D, Tabernero, J, Bernards, R, Friend, SH, Laurent-Puig, P, Medema, JP, Sadanandam, A, Wessels, L, Delorenzi, M, Kopetz, S, Vermeulen, L & Tejpar, S 2015, 'The consensus molecular subtypes of colorectal cancer', Nature medicine, vol. 21, no. 11, pp. 1350-1356. https://doi.org/10.1038/nm.3967

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title = "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-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.",

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

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year = "2015",

month = nov,

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AU - Guinney, Justin

AU - Dienstmann, Rodrigo

AU - Wang, Xin

AU - De Reyniès, Aurélien

AU - Schlicker, Andreas

AU - Soneson, Charlotte

AU - Marisa, Laetitia

AU - Roepman, Paul

AU - Nyamundanda, Gift

AU - Angelino, Paolo

AU - Bot, Brian M.

AU - Morris, Jeffrey S.

AU - Simon, Iris M.

AU - Gerster, Sarah

AU - Fessler, Evelyn

AU - De Sousa .E Melo, Felipe

AU - Missiaglia, Edoardo

AU - Ramay, Hena

AU - Barras, David

AU - Homicsko, Krisztian

AU - Maru, Dipen

AU - Manyam, Ganiraju C.

AU - Broom, Bradley

AU - Boige, Valerie

AU - Perez-Villamil, Beatriz

AU - Laderas, Ted

AU - Salazar, Ramon

AU - Gray, Joe W.

AU - Hanahan, Douglas

AU - Tabernero, Josep

AU - Bernards, Rene

AU - Friend, Stephen H.

AU - Laurent-Puig, Pierre

AU - Medema, Jan Paul

AU - Sadanandam, Anguraj

AU - Wessels, Lodewyk

AU - Delorenzi, Mauro

AU - Kopetz, Scott

AU - Vermeulen, Louis

AU - Tejpar, Sabine

PY - 2015/11/1

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N2 - 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.

AB - 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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The consensus molecular subtypes of colorectal cancer

Abstract

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