Comprehensive molecular characterization of gastric adenocarcinoma
Adam J. BassDepartment of Medical Oncology and the Center for Cancer Genome Discovery, Dana-Farber Cancer Institute, Boston, 02215, Massachusetts, USANatalie TasmanInstitute for Systems Biology, Seattle, 98109, Washington, USABrady BernardInstitute for Systems Biology, Seattle, 98109, Washington, USAVésteinn ThórssonInstitute for Systems Biology, Seattle, 98109, Washington, USARoger KramerInstitute for Systems Biology, Seattle, 98109, Washington, USAMichael MillerInstitute for Systems Biology, Seattle, 98109, Washington, USAIlya ShmulevichInstitute for Systems Biology, Seattle, 98109, Washington, USALisa IypeInstitute for Systems Biology, Seattle, 98109, Washington, USAHector RoviraInstitute for Systems Biology, Seattle, 98109, Washington, USARichard KreisbergInstitute for Systems Biology, Seattle, 98109, Washington, USASheila M. ReynoldsInstitute for Systems Biology, Seattle, 98109, Washington, USATimothy J. TricheUSC Epigenome Center, University of Southern California, Los Angeles, 90033, California, USAMoiz S. BootwallaUSC Epigenome Center, University of Southern California, Los Angeles, 90033, California, USAPhillip H. LaiUSC Epigenome Center, University of Southern California, Los Angeles, 90033, California, USAToshinori HinoueUSC Epigenome Center, University of Southern California, Los Angeles, 90033, California, USAHui ShenUSC Epigenome Center, University of Southern California, Los Angeles, 90033, California, USADaniel J. WeisenbergerUSC Epigenome Center, University of Southern California, Los Angeles, 90033, California, USADavid Van Den BergUSC Epigenome Center, University of Southern California, Los Angeles, 90033, California, USAPeter W. LairdUSC Epigenome Center, University of Southern California, Los Angeles, 90033, California, USAChristina CurtisDepartment of Preventive Medicine, University of Southern California, USC/Norris Comprehensive Cancer Center, Los Angeles, 90033, California, USANikolaus SchultzComputational Biology Center, Memorial Sloan-Kettering Cancer Center, New York, 10065, New York, USAJianjiong GaoComputational Biology Center, Memorial Sloan-Kettering Cancer Center, New York, 10065, New York, USANils WeinholdComputational Biology Center, Memorial Sloan-Kettering Cancer Center, New York, 10065, New York, USAYasin ŞenbabaoğluComputational Biology Center, Memorial Sloan-Kettering Cancer Center, New York, 10065, New York, USARileen SinhaComputational Biology Center, Memorial Sloan-Kettering Cancer Center, New York, 10065, New York, USAAnders JacobsenComputational Biology Center, Memorial Sloan-Kettering Cancer Center, New York, 10065, New York, USABenjamin GroßComputational Biology Center, Memorial Sloan-Kettering Cancer Center, New York, 10065, New York, USAGideon DresdnerComputational Biology Center, Memorial Sloan-Kettering Cancer Center, New York, 10065, New York, USARicardo RamírezComputational Biology Center, Memorial Sloan-Kettering Cancer Center, New York, 10065, New York, USAChris SanderComputational Biology Center, Memorial Sloan-Kettering Cancer Center, New York, 10065, New York, USAS. Onur SumerComputational Biology Center, Memorial Sloan-Kettering Cancer Center, New York, 10065, New York, USAr B. Arman AskoyComputational Biology Center, Memorial Sloan-Kettering Cancer Center, New York, 10065, New York, USAWilliam LeeComputational Biology Center, Memorial Sloan-Kettering Cancer Center, New York, 10065, New York, USAGiovanni CirielloComputational Biology Center, Memorial Sloan-Kettering Cancer Center, New York, 10065, New York, USAYichao SunComputational Biology Center, Memorial Sloan-Kettering Cancer Center, New York, 10065, New York, USARonglai ShenDepartment of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, 10065, New York, USAYelena Y. JanjigianDepartment of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA.,David P. KelsenDepartment of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA.,David P. KelsenDepartment of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, New York 10021, USA.,Haiyan A. LiCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 4S6, Canada.,Amanda ClarkeCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 4S6, Canada.,Noreen DhallaCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 4S6, Canada.,Andy ChuCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 4S6, Canada.,Andrew J. MungallCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 4S6, Canada.,Justin ChuCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 4S6, Canada.,Nina ThiessenCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 4S6, Canada.,Karen MungallCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 4S6, Canada.,Emilia L. LimCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 4S6, Canada.,Denise BrooksCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 4S6, Canada.,Reanne BowlbyCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 4S6, Canada.,Miruna BalasundaramCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 4S6, Canada.,Darlene LeeCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 4S6, Canada.,Angela TamCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 4S6, Canada.,Richard A. MooreCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 4S6, Canada.,Hye-Jung E. ChunCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 4S6, Canada.,Michael MayoCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 4S6, Canada.,A. Gordon RobertsonCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 4S6, Canada.,Eric ChuahCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 4S6, Canada.,Steven J.M. JonesCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 4S6, Canada.,Rebecca CarlsenCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 4S6, Canada.,Katayoon KasaianCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 4S6, Canada.,Marco A. MarraCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 4S6, Canada.,Payal SipahimalaniCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 4S6, Canada.,Yussanne MaCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 4S6, Canada.,Ranabir GuinCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 4S6, Canada.,Robert A. HoltCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 4S6, Canada.,Yaron S.N. ButterfieldCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 4S6, Canada.,Ka Ming NipCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 4S6, Canada.,Reanne BowlbyCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 4S6, Canada.,Adrian AllyCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 4S6, Canada.,Jacqueline E. ScheinCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 4S6, Canada.,İnanç BirolCanada’s Michael Smith Genome Sciences Centre, BC Cancer Agency, Vancouver, BC V5Z 4S6, Canada.,Lihua ZouThe Eli and Edythe L. Broad Institute, Cambridge, 02142, Massachusetts, USANils GehlenborgThe Eli and Edythe L. Broad Institute, Cambridge, 02142, Massachusetts, USAYingchun LiuThe Eli and Edythe L. Broad Institute, Cambridge, 02142, Massachusetts, USATravis ZackThe Eli and Edythe L. Broad Institute, Cambridge, 02142, Massachusetts, USAScott L. CarterThe Eli and Edythe L. Broad Institute, Cambridge, 02142, Massachusetts, USAJaegil KimDepartment of Pathology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, 138-736, South KoreaEric S. LanderThe Eli and Edythe L. Broad Institute, Cambridge, 02142, Massachusetts, USAPetar StojanovThe Eli and Edythe L. Broad Institute, Cambridge, 02142, Massachusetts, USABarbara TabakThe Eli and Edythe L. Broad Institute, Cambridge, 02142, Massachusetts, USAAndrew D. CherniackThe Eli and Edythe L. Broad Institute, Cambridge, 02142, Massachusetts, USAGordon SaksenaThe Eli and Edythe L. Broad Institute, Cambridge, 02142, Massachusetts, USABradley A. MurrayThe Eli and Edythe L. Broad Institute, Cambridge, 02142, Massachusetts, USARameen BeroukhimThe Eli and Edythe L. Broad Institute, Cambridge, 02142, Massachusetts, USALee LichtensteinThe Eli and Edythe L. Broad Institute, Cambridge, 02142, Massachusetts, USACarrie SougnezThe Eli and Edythe L. Broad Institute, Cambridge, 02142, Massachusetts, USAGad GetzThe Eli and Edythe L. Broad Institute, Cambridge, 02142, Massachusetts, USAChandra Sekhar PedamalluThe Eli and Edythe L. Broad Institute, Cambridge, 02142, Massachusetts, USAJuok ChoThe Eli and Edythe L. Broad Institute, Cambridge, 02142, Massachusetts, USAKristian CibulskisThe Eli and Edythe L. Broad Institute, Cambridge, 02142, Massachusetts, USADavid I. HeimanThe Eli and Edythe L. Broad Institute, Cambridge, 02142, Massachusetts, USADoug VoetThe Eli and Edythe L. Broad Institute, Cambridge, 02142, Massachusetts, USAJoonil JungThe Eli and Edythe L. Broad Institute, Cambridge, 02142, Massachusetts, USASheila FisherThe Eli and Edythe L. Broad Institute, Cambridge, 02142, Massachusetts, USAHailei ZhangThe Eli and Edythe L. Broad Institute, Cambridge, 02142, Massachusetts, USAScott FrazerThe Eli and Edythe L. Broad Institute, Cambridge, 02142, Massachusetts, USA
2014en
ABI
Аннотация
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. The Cancer Genome Atlas reports on molecular evaluation of 295 primary gastric adenocarcinomas and proposes a new classification of gastric cancers into 4 subtypes, which should help with clinical assessment and trials of targeted therapies. This contribution from The Cancer Genome Atlas (TCGA) project describes the molecular evaluation of 295 primary gastric adenocarcinomas. Based on the results, the authors propose a novel classification separating gastric cancers into four subtypes according to: Epstein–Barr virus positive status, microsatellite instability, chromosomal instability or genomic stability. Given the histologic and etiologic heterogeneity of gastric cancer identification of these subtypes, using a schema that can readily be applied to patient samples should help with patient stratification and trials of targeted therapies.
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