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

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