Comprehensive molecular characterization of gastric adenocarcinoma

Adam J. Bass; Vesteinn Thorsson; Ilya Shmulevich; Sheila M. Reynolds; Michael Miller; Brady Bernard; Toshinori Hinoue; Peter W. Laird; Christina Curtis; Hui Shen; Daniel J. Weisenberger; Nikolaus Schultz; Ronglai Shen; Nils Weinhold; David P. Kelsen; Reanne Bowlby; Andy Chu; Katayoon Kasaian; Andrew J. Mungall; A. Gordon Robertson; Payal Sipahimalani; Andrew D. Cherniack; Gad Getz; Yingchun Liu; Michael S. Noble; Chandra Pedamallu; Carrie Sougnez; Amaro Taylor-Weiner; Rehan Akbani; Ju Seog Lee; Wenbin Liu; Gordon B. Mills; Da Yang; Wei Zhang; Angeliki Pantazi; Michael Parfenov; Margaret Gulley; M. Blanca Piazuelo; Barbara G. Schneider; Jihun Kim; Alex Boussioutas; Margi Sheth; John A. Demchok; Charles S. Rabkin; Joseph E. Willis; Sam Ng; Katherine Garman; David G. Beer; Arjun Pennathur; Lihua Zou; Cancer Genome Atlas Research Network

doi:10.1038/nature13480

Comprehensive molecular characterization of gastric adenocarcinoma

Adam J. Bass, Vesteinn Thorsson, Ilya Shmulevich, Sheila M. Reynolds, Michael Miller, Brady Bernard, Toshinori Hinoue, Peter W. Laird, Christina Curtis, Hui Shen, Daniel J. Weisenberger, Nikolaus Schultz, Ronglai Shen, Nils Weinhold, David P. Kelsen, Reanne Bowlby, Andy Chu, Katayoon Kasaian, Andrew J. Mungall, A. Gordon RobertsonPayal Sipahimalani, Andrew D. Cherniack, Gad Getz, Yingchun Liu, Michael S. Noble, Chandra Pedamallu, Carrie Sougnez, Amaro Taylor-Weiner, Rehan Akbani, Ju Seog Lee, Wenbin Liu, Gordon B. Mills, Da Yang, Wei Zhang, Angeliki Pantazi, Michael Parfenov, Margaret Gulley, M. Blanca Piazuelo, Barbara G. Schneider, Jihun Kim, Alex Boussioutas, Margi Sheth, John A. Demchok, Charles S. Rabkin, Joseph E. Willis, Sam Ng, Katherine Garman, David G. Beer, Arjun Pennathur, Lihua Zou, Cancer Genome Atlas Research Network

Biochemistry and Molecular Genetics

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

4345 Scopus citations

Abstract

Gastric cancer is a leading cause of cancer deaths, but analysis of its molecular and clinical characteristics has been complicated by histological and aetiological heterogeneity. Here we describe a comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project. We propose a molecular classification dividing gastric cancer into four subtypes: tumours positive for Epstein-Barr virus, which display recurrent PIK3CA mutations, extreme DNA hypermethylation, and amplification of JAK2, CD274 (also known as PD-L1) and PDCD1LG2 (also known as PD-L2); microsatellite unstable tumours, which show elevated mutation rates, including mutations of genes encoding targetable oncogenic signalling proteins; genomically stable tumours, which are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins; and tumours with chromosomal instability, which show marked aneuploidy and focal amplification of receptor tyrosine kinases. Identification of these subtypes provides a roadmap for patient stratification and trials of targeted therapies.

Original language	English (US)
Pages (from-to)	202-209
Number of pages	8
Journal	Nature
Volume	513
Issue number	7517
DOIs	https://doi.org/10.1038/nature13480
State	Published - Sep 11 2014

ASJC Scopus subject areas

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UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Bass, A. J., Thorsson, V., Shmulevich, I., Reynolds, S. M., Miller, M., Bernard, B., Hinoue, T., Laird, P. W., Curtis, C., Shen, H., Weisenberger, D. J., Schultz, N., Shen, R., Weinhold, N., Kelsen, D. P., Bowlby, R., Chu, A., Kasaian, K., Mungall, A. J., ... Cancer Genome Atlas Research Network (2014). Comprehensive molecular characterization of gastric adenocarcinoma. Nature, 513(7517), 202-209. https://doi.org/10.1038/nature13480

@article{da9f30ccd2ae4df6b9532ef5eb1a9a17,

title = "Comprehensive molecular characterization of gastric adenocarcinoma",

abstract = "Gastric cancer is a leading cause of cancer deaths, but analysis of its molecular and clinical characteristics has been complicated by histological and aetiological heterogeneity. Here we describe a comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project. We propose a molecular classification dividing gastric cancer into four subtypes: tumours positive for Epstein-Barr virus, which display recurrent PIK3CA mutations, extreme DNA hypermethylation, and amplification of JAK2, CD274 (also known as PD-L1) and PDCD1LG2 (also known as PD-L2); microsatellite unstable tumours, which show elevated mutation rates, including mutations of genes encoding targetable oncogenic signalling proteins; genomically stable tumours, which are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins; and tumours with chromosomal instability, which show marked aneuploidy and focal amplification of receptor tyrosine kinases. Identification of these subtypes provides a roadmap for patient stratification and trials of targeted therapies.",

author = "Bass, {Adam J.} and Vesteinn Thorsson and Ilya Shmulevich and Reynolds, {Sheila M.} and Michael Miller and Brady Bernard and Toshinori Hinoue and Laird, {Peter W.} and Christina Curtis and Hui Shen and Weisenberger, {Daniel J.} and Nikolaus Schultz and Ronglai Shen and Nils Weinhold and Kelsen, {David P.} and Reanne Bowlby and Andy Chu and Katayoon Kasaian and Mungall, {Andrew J.} and Robertson, {A. Gordon} and Payal Sipahimalani and Cherniack, {Andrew D.} and Gad Getz and Yingchun Liu and Noble, {Michael S.} and Chandra Pedamallu and Carrie Sougnez and Amaro Taylor-Weiner and Rehan Akbani and Lee, {Ju Seog} and Wenbin Liu and Mills, {Gordon B.} and Da Yang and Wei Zhang and Angeliki Pantazi and Michael Parfenov and Margaret Gulley and Piazuelo, {M. Blanca} and Schneider, {Barbara G.} and Jihun Kim and Alex Boussioutas and Margi Sheth and Demchok, {John A.} and Rabkin, {Charles S.} and Willis, {Joseph E.} and Sam Ng and Katherine Garman and Beer, {David G.} and Arjun Pennathur and Lihua Zou and {Cancer Genome Atlas Research Network}",

year = "2014",

month = sep,

day = "11",

doi = "10.1038/nature13480",

language = "English (US)",

volume = "513",

pages = "202--209",

journal = "Nature",

issn = "0028-0836",

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Bass, AJ, Thorsson, V, Shmulevich, I, Reynolds, SM, Miller, M, Bernard, B, Hinoue, T, Laird, PW, Curtis, C, Shen, H, Weisenberger, DJ, Schultz, N, Shen, R, Weinhold, N, Kelsen, DP, Bowlby, R, Chu, A, Kasaian, K, Mungall, AJ, Robertson, AG, Sipahimalani, P, Cherniack, AD, Getz, G, Liu, Y, Noble, MS, Pedamallu, C, Sougnez, C, Taylor-Weiner, A, Akbani, R, Lee, JS, Liu, W, Mills, GB, Yang, D, Zhang, W, Pantazi, A, Parfenov, M, Gulley, M, Piazuelo, MB, Schneider, BG, Kim, J, Boussioutas, A, Sheth, M, Demchok, JA, Rabkin, CS, Willis, JE, Ng, S, Garman, K, Beer, DG, Pennathur, A, Zou, L & Cancer Genome Atlas Research Network 2014, 'Comprehensive molecular characterization of gastric adenocarcinoma', Nature, vol. 513, no. 7517, pp. 202-209. https://doi.org/10.1038/nature13480

TY - JOUR

T1 - Comprehensive molecular characterization of gastric adenocarcinoma

AU - Bass, Adam J.

AU - Thorsson, Vesteinn

AU - Shmulevich, Ilya

AU - Reynolds, Sheila M.

AU - Miller, Michael

AU - Bernard, Brady

AU - Hinoue, Toshinori

AU - Laird, Peter W.

AU - Curtis, Christina

AU - Shen, Hui

AU - Weisenberger, Daniel J.

AU - Schultz, Nikolaus

AU - Shen, Ronglai

AU - Weinhold, Nils

AU - Kelsen, David P.

AU - Bowlby, Reanne

AU - Chu, Andy

AU - Kasaian, Katayoon

AU - Mungall, Andrew J.

AU - Robertson, A. Gordon

AU - Sipahimalani, Payal

AU - Cherniack, Andrew D.

AU - Getz, Gad

AU - Liu, Yingchun

AU - Noble, Michael S.

AU - Pedamallu, Chandra

AU - Sougnez, Carrie

AU - Taylor-Weiner, Amaro

AU - Akbani, Rehan

AU - Lee, Ju Seog

AU - Liu, Wenbin

AU - Mills, Gordon B.

AU - Yang, Da

AU - Zhang, Wei

AU - Pantazi, Angeliki

AU - Parfenov, Michael

AU - Gulley, Margaret

AU - Piazuelo, M. Blanca

AU - Schneider, Barbara G.

AU - Kim, Jihun

AU - Boussioutas, Alex

AU - Sheth, Margi

AU - Demchok, John A.

AU - Rabkin, Charles S.

AU - Willis, Joseph E.

AU - Ng, Sam

AU - Garman, Katherine

AU - Beer, David G.

AU - Pennathur, Arjun

AU - Zou, Lihua

AU - Cancer Genome Atlas Research Network

PY - 2014/9/11

Y1 - 2014/9/11

N2 - Gastric cancer is a leading cause of cancer deaths, but analysis of its molecular and clinical characteristics has been complicated by histological and aetiological heterogeneity. Here we describe a comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project. We propose a molecular classification dividing gastric cancer into four subtypes: tumours positive for Epstein-Barr virus, which display recurrent PIK3CA mutations, extreme DNA hypermethylation, and amplification of JAK2, CD274 (also known as PD-L1) and PDCD1LG2 (also known as PD-L2); microsatellite unstable tumours, which show elevated mutation rates, including mutations of genes encoding targetable oncogenic signalling proteins; genomically stable tumours, which are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins; and tumours with chromosomal instability, which show marked aneuploidy and focal amplification of receptor tyrosine kinases. Identification of these subtypes provides a roadmap for patient stratification and trials of targeted therapies.

AB - Gastric cancer is a leading cause of cancer deaths, but analysis of its molecular and clinical characteristics has been complicated by histological and aetiological heterogeneity. Here we describe a comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project. We propose a molecular classification dividing gastric cancer into four subtypes: tumours positive for Epstein-Barr virus, which display recurrent PIK3CA mutations, extreme DNA hypermethylation, and amplification of JAK2, CD274 (also known as PD-L1) and PDCD1LG2 (also known as PD-L2); microsatellite unstable tumours, which show elevated mutation rates, including mutations of genes encoding targetable oncogenic signalling proteins; genomically stable tumours, which are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins; and tumours with chromosomal instability, which show marked aneuploidy and focal amplification of receptor tyrosine kinases. Identification of these subtypes provides a roadmap for patient stratification and trials of targeted therapies.

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UR - http://www.scopus.com/inward/citedby.url?scp=84907270779&partnerID=8YFLogxK

U2 - 10.1038/nature13480

DO - 10.1038/nature13480

M3 - Article

C2 - 25079317

AN - SCOPUS:84907270779

SN - 0028-0836

VL - 513

SP - 202

EP - 209

JO - Nature

JF - Nature

IS - 7517

ER -

Comprehensive molecular characterization of gastric adenocarcinoma

Abstract

ASJC Scopus subject areas

UN SDGs

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