Exome sequencing of gastric adenocarcinoma identifies recurrent somatic mutations in cell adhesion and chromatin remodeling genes.

Published

Journal Article

Gastric cancer is a major cause of global cancer mortality. We surveyed the spectrum of somatic alterations in gastric cancer by sequencing the exomes of 15 gastric adenocarcinomas and their matched normal DNAs. Frequently mutated genes in the adenocarcinomas included TP53 (11/15 tumors), PIK3CA (3/15) and ARID1A (3/15). Cell adhesion was the most enriched biological pathway among the frequently mutated genes. A prevalence screening confirmed mutations in FAT4, a cadherin family gene, in 5% of gastric cancers (6/110) and FAT4 genomic deletions in 4% (3/83) of gastric tumors. Frequent mutations in chromatin remodeling genes (ARID1A, MLL3 and MLL) also occurred in 47% of the gastric cancers. We detected ARID1A mutations in 8% of tumors (9/110), which were associated with concurrent PIK3CA mutations and microsatellite instability. In functional assays, we observed both FAT4 and ARID1A to exert tumor-suppressor activity. Somatic inactivation of FAT4 and ARID1A may thus be key tumorigenic events in a subset of gastric cancers.

Full Text

Duke Authors

Cited Authors

  • Zang, ZJ; Cutcutache, I; Poon, SL; Zhang, SL; McPherson, JR; Tao, J; Rajasegaran, V; Heng, HL; Deng, N; Gan, A; Lim, KH; Ong, CK; Huang, D; Chin, SY; Tan, IB; Ng, CCY; Yu, W; Wu, Y; Lee, M; Wu, J; Poh, D; Wan, WK; Rha, SY; So, J; Salto-Tellez, M; Yeoh, KG; Wong, WK; Zhu, Y-J; Futreal, PA; Pang, B; Ruan, Y; Hillmer, AM; Bertrand, D; Nagarajan, N; Rozen, S; Teh, BT; Tan, P

Published Date

  • May 2012

Published In

Volume / Issue

  • 44 / 5

Start / End Page

  • 570 - 574

PubMed ID

  • 22484628

Pubmed Central ID

  • 22484628

Electronic International Standard Serial Number (EISSN)

  • 1546-1718

Digital Object Identifier (DOI)

  • 10.1038/ng.2246

Language

  • eng

Conference Location

  • United States