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한빛사논문, 상위피인용논문
- 조회4,532
Nat. Med., Published online 20 April 2015 | doi:10.1038/nm.3850
Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes
Abstract
Razvan Cristescu1,12, Jeeyun Lee2,12, Michael Nebozhyn1,12, Kyoung-Mee Kim3,12, Jason C Ting4, Swee Seong Wong4, Jiangang Liu4, Yong Gang Yue4, Jian Wang4, Kun Yu4,11, Xiang S Ye4, In-Gu Do3, Shawn Liu5, Lara Gong5, Jake Fu6, Jason Gang Jin6, Min Gew Choi7, Tae Sung Sohn7, Joon Ho Lee7, Jae Moon Bae7, Seung Tae Kim2, Se Hoon Park2, Insuk Sohn8, Sin-Ho Jung8, Patrick Tan9,10, Ronghua Chen1, James Hardwick1,11, Won Ki Kang2, Mark Ayers1, Dai Hongyue1,11, Christoph Reinhard4, Andrey Loboda1, Sung Kim7 & Amit Aggarwal4
1Department of Genetics and Pharmacogenomics, Merck Research Laboratories, Merck Sharpe & Dohme, Boston, Massachusetts, USA. 2Department of Medicine, Division of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. 3Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. 4Lilly Research Labs, Eli Lilly & Co, Indianapolis, Indiana, USA. 5BGI Tech Solutions, Hong Kong, China. 6Shanghai Biocorp, Shanghai, China. 7Department of Surgery, Gastric Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. 8Biostatistics and Clinical Epidemiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. 9Program in Cancer and Stem Cell Biology, Duke-National University of Singapore (NUS) Graduate Medical School, Singapore. 10Genome Institute of Singapore, Singapore. 11Present addresses: Novartis Institute for Biomedical Research, Boston, Massachusetts, USA (K.Y.); Pfizer, San Diego, California, USA (J.H.) M2Gen, Tampa, Florida, USA (H.D.). 12These authors contributed equally to this article.
Correspondence to : Andrey Loboda or Sung Kim or Amit Aggarwal
Abstract
Gastric cancer, a leading cause of cancer-related deaths, is a heterogeneous disease. We aim to establish clinically relevant molecular subtypes that would encompass this heterogeneity and provide useful clinical information. We use gene expression data to describe four molecular subtypes linked to distinct patterns of molecular alterations, disease progression and prognosis. The mesenchymal-like type includes diffuse-subtype tumors with the worst prognosis, the tendency to occur at an earlier age and the highest recurrence frequency (63%) of the four subtypes. Microsatellite-unstable tumors are hyper-mutated intestinal-subtype tumors occurring in the antrum; these have the best overall prognosis and the lowest frequency of recurrence (22%) of the four subtypes. The tumor protein 53 (TP53)-active and TP53-inactive types include patients with intermediate prognosis and recurrence rates (with respect to the other two subtypes), with the TP53-active group showing better prognosis. We describe key molecular alterations in each of the four subtypes using targeted sequencing and genome-wide copy number microarrays. We validate these subtypes in independent cohorts in order to provide a consistent and unified framework for further clinical and preclinical translational research.
논문정보
- Research article
- 2015년 04월 (BRIC 등록일 2015-04-24)
- 국내(교신)+국외 연구진
- 의약학 > 종양의학
- 60회 이상 인용된 논문 (상위피인용논문 등록일 2017-01-05)
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