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Nat Med. 2015 May;21(5):449-56. doi: 10.1038/nm.3850. Epub 2015 Apr 20.

Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes.

Author information

1
Department of Genetics and Pharmacogenomics, Merck Research Laboratories, Merck Sharpe &Dohme, Boston, Massachusetts, USA.
2
Department of Medicine, Division of Hematology-Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
3
Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
4
Lilly Research Labs, Eli Lilly &Co, Indianapolis, Indiana, USA.
5
BGI Tech Solutions, Hong Kong, China.
6
Shanghai Biocorp, Shanghai, China.
7
Department of Surgery, Gastric Cancer Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
8
Biostatistics and Clinical Epidemiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
9
1] Program in Cancer and Stem Cell Biology, Duke-National University of Singapore (NUS) Graduate Medical School, Singapore. [2] Genome Institute of Singapore, Singapore.

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.

PMID:
25894828
DOI:
10.1038/nm.3850
[Indexed for MEDLINE]

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