Comprehensive molecular characterization of gastric adenocarcinoma

The Cancer Genome Atlas Research Network

doi:10.1038/nature13480

Comprehensive molecular characterization of gastric adenocarcinoma

The Cancer Genome Atlas Research Network

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

5682 Citations (Scopus)

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
Pages (from-to)	202-209
Number of pages	8
Journal	Nature
Volume	513
Issue number	7517
DOIs	https://doi.org/10.1038/nature13480
Publication status	Published - 11 Sept 2014
Externally published	Yes

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SDG 3 Good Health and Well-being

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10.1038/nature13480Licence: CC BY-NC-SA

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@article{ec1543d0359043d88e6fdca8ed631a95,

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 Raphael, \{Benjamin J.\} and Wu, \{Hsin Ta\} and Robert Odze and Kim, \{Hark K.\} and Jay Bowen and Leraas, \{Kristen M.\} and Lichtenberg, \{Tara M.\} and Stephanie Weaver and Michael McLellan and Maciej Wiznerowicz and Ryo Sakai and Lawrence, \{Michael S.\} and Kristian Cibulskis and Lee Lichtenstein and Sheila Fisher and Gabriel, \{Stacey B.\} and Lander, \{Eric S.\} and Li Ding and Beifang Niu and Adrian Ally and Miruna Balasundaram and Inanc Birol and Denise Brooks and Butterfield, \{Yaron S.N.\} and Rebecca Carlsen and Justin Chu and Eric Chuah and Chun, \{Hye Jung E.\} and Amanda Clarke and Noreen Dhalla and Ranabir Guin and Holt, \{Robert A.\} and Jones, \{Steven J.M.\} and Darlene Lee and Li, \{Haiyan A.\} and Emilia Lim and Yussanne Ma and Marra, \{Marco A.\} and Michael Mayo and Moore, \{Richard A.\} and Mungall, \{Karen L.\} and Nip, \{Ka Ming\} and Schein, \{Jacqueline E.\} and Angela Tam and Nina Thiessen and Rameen Beroukhim and Carter, \{Scott L.\} and Juok Cho and Daniel DiCara and Scott Frazer and Nils Gehlenborg and Heiman, \{David I.\} and Joonil Jung and Jaegil Kim and Pei Lin and Matthew Meyerson and Ojesina, \{Akinyemi I.\} and Pedamallu, \{Chandra Sekhar\} and Gordon Saksena and Schumacher, \{Steven E.\} and Petar Stojanov and Barbara Tabak and Doug Voet and Mara Rosenberg and Zack, \{Travis I.\} and Hailei Zhang and Lihua Zou and Alexei Protopopov and Netty Santoso and Semin Lee and Jianhua Zhang and Mahadeshwar, \{Harshad S.\} and Jiabin Tang and Xiaojia Ren and Sahil Seth and Lixing Yang and Xu, \{Andrew W.\} and Xingzhi Song and Ruibin Xi and Bristow, \{Christopher A.\} and Angela Hadjipanayis and Jonathan Seidman and Lynda Chin and Park, \{Peter J.\} and Raju Kucherlapati and Shiyun Ling and Arvind Rao and Weinstein, \{John N.\} and Kim, \{Sang Bae\} and Yiling Lu and Bootwalla, \{Moiz S.\} and Lai, \{Phillip H.\} and Timothy Triche and \{Van Den Berg\}, \{David J.\} and Baylin, \{Stephen B.\} and Herman, \{James G.\} and Murray, \{Bradley A.\} and Askoy, \{B. Arman\} and Giovanni Ciriello and Gideon Dresdner and Jianjiong Gao and Benjamin Gross and Anders Jacobsen and William Lee and Ricardo Ramirez and Chris Sander and Yasin Senbabaoglu and Rileen Sinha and Sumer, \{S. Onur\} and Yichao Sun and Lisa Iype and Kramer, \{Roger W.\} and Richard Kreisberg and Hector Rovira and Natalie Tasman and David Haussler and Stuart, \{Josh M.\} and Verhaak, \{Roeland G.W.\} and Leiserson, \{Mark D.M.\} and Taylor, \{Barry S.\} and Black, \{Aaron D.\} and Carney, \{Julie Ann\} and Gastier-Foster, \{Julie M.\} and Carmen Helsel and Cynthia McAllister and Ramirez, \{Nilsa C.\} and Tabler, \{Teresa R.\} and Lisa Wise and Erik Zmuda and Robert Penny and Daniel Crain and Johanna Gardner and Kevin Lau and Erin Curely and David Mallery and Scott Morris and Joseph Paulauskis and Troy Shelton and Candace Shelton and Mark Sherman and Christopher Benz and Lee, \{Jae Hyuk\} and Konstantin Fedosenko and Georgy Manikhas and Olga Potapova and Olga Voronina and Dmitry Belyaev and Oleg Dolzhansky and Rathmell, \{W. Kimryn\} and Jakub Brzezinski and Matthew Ibbs and Konstanty Korski and Witold Kycler and Radoslaw {\L}a{\'z}niak and Ewa Leporowska and Andrzej Mackiewicz and Dawid Murawa and Pawel Murawa and Arkadiusz Spycha{\l}a and Suchorska, \{Wiktoria M.\} and Honorata Tatka and Marek Teresiak and Raafat Abdel-Misih and Joseph Bennett and Jennifer Brown and Mary Iacocca and Brenda Rabeno and Kwon, \{Sun Young\} and Ariane Kemkes and Erin Curley and Iakovina Alexopoulou and Jay Engel and John Bartlett and Monique Albert and Park, \{Do Youn\} and Rajiv Dhir and James Luketich and Rodney Landreneau and Janjigian, \{Yelena Y.\} and Eunjung Cho and Marc Ladanyi and Laura Tang and McCall, \{Shannon J.\} and Park, \{Young S.\} and Cheong, \{Jae Ho\} and Jaffer Ajani and Camargo, \{M. Constanza\} and Shelley Alonso and Brenda Ayala and Jensen, \{Mark A.\} and Todd Pihl and Rohini Raman and Jessica Walton and Yunhu Wan and Greg Eley and Shaw, \{Kenna R.Mills\} and Roy Tarnuzzer and Zhining Wang and Liming Yang and Zenklusen, \{Jean Claude\} and Tanja Davidsen and \{The Cancer Genome Atlas Research Network\}",

year = "2014",

month = sep,

day = "11",

doi = "10.1038/nature13480",

language = "English",

volume = "513",

pages = "202--209",

journal = "Nature",

issn = "0028-0836",

publisher = "Nature Publishing Group",

number = "7517",

}

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 - Raphael, Benjamin J.

AU - Wu, Hsin Ta

AU - Odze, Robert

AU - Kim, Hark K.

AU - Bowen, Jay

AU - Leraas, Kristen M.

AU - Lichtenberg, Tara M.

AU - Weaver, Stephanie

AU - McLellan, Michael

AU - Wiznerowicz, Maciej

AU - Sakai, Ryo

AU - Lawrence, Michael S.

AU - Cibulskis, Kristian

AU - Lichtenstein, Lee

AU - Fisher, Sheila

AU - Gabriel, Stacey B.

AU - Lander, Eric S.

AU - Ding, Li

AU - Niu, Beifang

AU - Ally, Adrian

AU - Balasundaram, Miruna

AU - Birol, Inanc

AU - Brooks, Denise

AU - Butterfield, Yaron S.N.

AU - Carlsen, Rebecca

AU - Chu, Justin

AU - Chuah, Eric

AU - Chun, Hye Jung E.

AU - Clarke, Amanda

AU - Dhalla, Noreen

AU - Guin, Ranabir

AU - Holt, Robert A.

AU - Jones, Steven J.M.

AU - Lee, Darlene

AU - Li, Haiyan A.

AU - Lim, Emilia

AU - Ma, Yussanne

AU - Marra, Marco A.

AU - Mayo, Michael

AU - Moore, Richard A.

AU - Mungall, Karen L.

AU - Nip, Ka Ming

AU - Schein, Jacqueline E.

AU - Tam, Angela

AU - Thiessen, Nina

AU - Beroukhim, Rameen

AU - Carter, Scott L.

AU - Cho, Juok

AU - DiCara, Daniel

AU - Frazer, Scott

AU - Gehlenborg, Nils

AU - Heiman, David I.

AU - Jung, Joonil

AU - Kim, Jaegil

AU - Lin, Pei

AU - Meyerson, Matthew

AU - Ojesina, Akinyemi I.

AU - Pedamallu, Chandra Sekhar

AU - Saksena, Gordon

AU - Schumacher, Steven E.

AU - Stojanov, Petar

AU - Tabak, Barbara

AU - Voet, Doug

AU - Rosenberg, Mara

AU - Zack, Travis I.

AU - Zhang, Hailei

AU - Zou, Lihua

AU - Protopopov, Alexei

AU - Santoso, Netty

AU - Lee, Semin

AU - Zhang, Jianhua

AU - Mahadeshwar, Harshad S.

AU - Tang, Jiabin

AU - Ren, Xiaojia

AU - Seth, Sahil

AU - Yang, Lixing

AU - Xu, Andrew W.

AU - Song, Xingzhi

AU - Xi, Ruibin

AU - Bristow, Christopher A.

AU - Hadjipanayis, Angela

AU - Seidman, Jonathan

AU - Chin, Lynda

AU - Park, Peter J.

AU - Kucherlapati, Raju

AU - Ling, Shiyun

AU - Rao, Arvind

AU - Weinstein, John N.

AU - Kim, Sang Bae

AU - Lu, Yiling

AU - Bootwalla, Moiz S.

AU - Lai, Phillip H.

AU - Triche, Timothy

AU - Van Den Berg, David J.

AU - Baylin, Stephen B.

AU - Herman, James G.

AU - Murray, Bradley A.

AU - Askoy, B. Arman

AU - Ciriello, Giovanni

AU - Dresdner, Gideon

AU - Gao, Jianjiong

AU - Gross, Benjamin

AU - Jacobsen, Anders

AU - Lee, William

AU - Ramirez, Ricardo

AU - Sander, Chris

AU - Senbabaoglu, Yasin

AU - Sinha, Rileen

AU - Sumer, S. Onur

AU - Sun, Yichao

AU - Iype, Lisa

AU - Kramer, Roger W.

AU - Kreisberg, Richard

AU - Rovira, Hector

AU - Tasman, Natalie

AU - Haussler, David

AU - Stuart, Josh M.

AU - Verhaak, Roeland G.W.

AU - Leiserson, Mark D.M.

AU - Taylor, Barry S.

AU - Black, Aaron D.

AU - Carney, Julie Ann

AU - Gastier-Foster, Julie M.

AU - Helsel, Carmen

AU - McAllister, Cynthia

AU - Ramirez, Nilsa C.

AU - Tabler, Teresa R.

AU - Wise, Lisa

AU - Zmuda, Erik

AU - Penny, Robert

AU - Crain, Daniel

AU - Gardner, Johanna

AU - Lau, Kevin

AU - Curely, Erin

AU - Mallery, David

AU - Morris, Scott

AU - Paulauskis, Joseph

AU - Shelton, Troy

AU - Shelton, Candace

AU - Sherman, Mark

AU - Benz, Christopher

AU - Lee, Jae Hyuk

AU - Fedosenko, Konstantin

AU - Manikhas, Georgy

AU - Potapova, Olga

AU - Voronina, Olga

AU - Belyaev, Dmitry

AU - Dolzhansky, Oleg

AU - Rathmell, W. Kimryn

AU - Brzezinski, Jakub

AU - Ibbs, Matthew

AU - Korski, Konstanty

AU - Kycler, Witold

AU - Łaźniak, Radoslaw

AU - Leporowska, Ewa

AU - Mackiewicz, Andrzej

AU - Murawa, Dawid

AU - Murawa, Pawel

AU - Spychała, Arkadiusz

AU - Suchorska, Wiktoria M.

AU - Tatka, Honorata

AU - Teresiak, Marek

AU - Abdel-Misih, Raafat

AU - Bennett, Joseph

AU - Brown, Jennifer

AU - Iacocca, Mary

AU - Rabeno, Brenda

AU - Kwon, Sun Young

AU - Kemkes, Ariane

AU - Curley, Erin

AU - Alexopoulou, Iakovina

AU - Engel, Jay

AU - Bartlett, John

AU - Albert, Monique

AU - Park, Do Youn

AU - Dhir, Rajiv

AU - Luketich, James

AU - Landreneau, Rodney

AU - Janjigian, Yelena Y.

AU - Cho, Eunjung

AU - Ladanyi, Marc

AU - Tang, Laura

AU - McCall, Shannon J.

AU - Park, Young S.

AU - Cheong, Jae Ho

AU - Ajani, Jaffer

AU - Camargo, M. Constanza

AU - Alonso, Shelley

AU - Ayala, Brenda

AU - Jensen, Mark A.

AU - Pihl, Todd

AU - Raman, Rohini

AU - Walton, Jessica

AU - Wan, Yunhu

AU - Eley, Greg

AU - Shaw, Kenna R.Mills

AU - Tarnuzzer, Roy

AU - Wang, Zhining

AU - Yang, Liming

AU - Zenklusen, Jean Claude

AU - Davidsen, Tanja

AU - The 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.

UR - https://www.scopus.com/pages/publications/84907270779

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

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