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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Cristescu, R; Lee, J; Nebozhyn, M; Kim, K-M; Ting, JC; Wong, SS; Liu, J; Yue, YG; Wang, J; Yu, K; Ye, XS; Do, I-G; Liu, S; Gong, L; Fu, J; Jin, JG; Choi, MG; Sohn, TS; Lee, JH; Bae, JM; Kim, ST; Park, SH; Sohn, I; Jung, S-H; Tan, P; Chen, R; Hardwick, J; Kang, WK; Ayers, M; Hongyue, D; Reinhard, C; Loboda, A; Kim, S; Aggarwal, A

Published Date

  • May 2015

Published In

Volume / Issue

  • 21 / 5

Start / End Page

  • 449 - 456

PubMed ID

  • 25894828

Pubmed Central ID

  • 25894828

Electronic International Standard Serial Number (EISSN)

  • 1546-170X

Digital Object Identifier (DOI)

  • 10.1038/nm.3850

Language

  • eng

Conference Location

  • United States