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

Authors
 Zhi Jiang Zang  ;  Ioana Cutcutache  ;  Song Ling Poon  ;  Shen Li Zhang  ;  John R McPherson  ;  Jiong Tao  ;  Vikneswari Rajasegaran  ;  Hong Lee Heng  ;  Niantao Deng  ;  Anna Gan  ;  Kiat Hon Lim  ;  Choon Kiat Ong  ;  DaChuan Huang  ;  Sze Yung Chin  ;  Iain Beehuat Tan  ;  Cedric Chuan Young Ng  ;  Willie Yu  ;  Yingting Wu  ;  Minghui Lee  ;  Jeanie Wu  ;  Dianne Poh  ;  Wei Keat Wan  ;  Sun Young Rha  ;  Jimmy So  ;  Manuel Salto-Tellez  ;  Khay Guan Yeoh  ;  Wai Keong Wong  ;  Yi-Jun Zhu  ;  P Andrew Futreal  ;  Brendan Pang  ;  Yijun Ruan  ;  Axel M Hillmer  ;  Denis Bertrand  ;  Niranjan Nagarajan  ;  Steve Rozen  ;  Bin Tean Teh  ;  Patrick Tan 
Citation
 Nature Genetics, Vol.44(5) : 570-574, 2012 
Journal Title
 Nature Genetics 
ISSN
 1061-4036 
Issue Date
2012
Abstract
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.
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/91503
DOI
10.1038/ng.2246
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실)
Yonsei Authors
라선영(Rha, Sun Young)
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Full Text
http://www.nature.com/ng/journal/v44/n5/full/ng.2246.html
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