title: Exome sequencing of gastric adenocarcinoma identifies recurrent  somatic mutations in cell adhesion and chromatin remodeling genes.
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.
authors.affiliation: Cellular and Molecular Research, National Cancer Centre, Singapore.
authors.forename: Zhi Jiang
authors.initials: ZJ
authors.lastname: Zang
authors.forename: Ioana
authors.initials: I
authors.lastname: Cutcutache
authors.forename: Song Ling
authors.initials: SL
authors.lastname: Poon
authors.forename: Shen Li
authors.initials: SL
authors.lastname: Zhang
authors.forename: John R
authors.initials: JR
authors.lastname: McPherson
authors.forename: Jiong
authors.initials: J
authors.lastname: Tao
authors.forename: Vikneswari
authors.initials: V
authors.lastname: Rajasegaran
authors.forename: Hong Lee
authors.initials: HL
authors.lastname: Heng
authors.forename: Niantao
authors.initials: N
authors.lastname: Deng
authors.forename: Anna
authors.initials: A
authors.lastname: Gan
authors.forename: Kiat Hon
authors.initials: KH
authors.lastname: Lim
authors.forename: Choon Kiat
authors.initials: CK
authors.lastname: Ong
authors.forename: DaChuan
authors.initials: D
authors.lastname: Huang
authors.forename: Sze Yung
authors.initials: SY
authors.lastname: Chin
authors.forename: Iain Beehuat
authors.initials: IB
authors.lastname: Tan
authors.forename: Cedric Chuan Young
authors.initials: CC
authors.lastname: Ng
authors.forename: Willie
authors.initials: W
authors.lastname: Yu
authors.forename: Yingting
authors.initials: Y
authors.lastname: Wu
authors.forename: Minghui
authors.initials: M
authors.lastname: Lee
authors.forename: Jeanie
authors.initials: J
authors.lastname: Wu
authors.forename: Dianne
authors.initials: D
authors.lastname: Poh
authors.forename: Wei Keat
authors.initials: WK
authors.lastname: Wan
authors.forename: Sun Young
authors.initials: SY
authors.lastname: Rha
authors.forename: Jimmy
authors.initials: J
authors.lastname: So
authors.forename: Manuel
authors.initials: M
authors.lastname: Salto-Tellez
authors.forename: Khay Guan
authors.initials: KG
authors.lastname: Yeoh
authors.forename: Wai Keong
authors.initials: WK
authors.lastname: Wong
authors.forename: Yi-Jun
authors.initials: YJ
authors.lastname: Zhu
authors.forename: P Andrew
authors.initials: PA
authors.lastname: Futreal
authors.forename: Brendan
authors.initials: B
authors.lastname: Pang
authors.forename: Yijun
authors.initials: Y
authors.lastname: Ruan
authors.forename: Axel M
authors.initials: AM
authors.lastname: Hillmer
authors.forename: Denis
authors.initials: D
authors.lastname: Bertrand
authors.forename: Niranjan
authors.initials: N
authors.lastname: Nagarajan
authors.forename: Steve
authors.initials: S
authors.lastname: Rozen
authors.forename: Bin Tean
authors.initials: BT
authors.lastname: Teh
authors.forename: Patrick
authors.initials: P
authors.lastname: Tan
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D016022:Case-Control Studies; D002448:Cell Adhesion / Q000235:genetics*; D042002:Chromatin Assembly and Disassembly / Q000235:genetics*; D004247:DNA / Q000235:genetics; D059472:Exome / Q000235:genetics*; D005753:Gastric Mucosa / Q000378:metabolism; D016147:Genes, Tumor Suppressor; D006801:Humans; D053842:Microsatellite Instability; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017422:Sequence Analysis, DNA; D013274:Stomach Neoplasms / Q000235:genetics*
chemical_list: D004247:DNA