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

Molecular Cancer Research

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

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
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
Publication status	Published - Nov 2015

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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

@article{083ae70f076d44548ba7adef7b8b580f,

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",

year = "2015",

month = nov,

doi = "10.1038/nm.3967",

language = "English",

volume = "21",

pages = "1350--1356",

journal = "Nature Medicine",

issn = "1078-8956",

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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, 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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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

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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.

U2 - 10.1038/nm.3967

DO - 10.1038/nm.3967

M3 - Article

C2 - 26457759

SN - 1078-8956

VL - 21

SP - 1350

EP - 1356

JO - Nature Medicine

JF - Nature Medicine

IS - 11

ER -

The consensus molecular subtypes of colorectal cancer

Abstract

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