Details

Autor(en) / Beteiligte

• ZHI JIANG ZANG
• CUTCUTACHE, Ioana
• HON LIM, Kiat
• KIAT ONG, Choon
• HUANG, Dachuan
• YUNG CHIN, Sze
• BEEHUAT TAN, Lain
• CHUAN YOUNG NG, Cedric
• WILLIE YU
• YINGTING WU
• LEE, Minghui
• WU, Jeanie
• POON, Song Ling
• POH, Dianne
• KEAT WAN, Wei
• YOUNG RHA, Sun
• SO, Jimmy
• SALTO-TELLEZ, Manuel
• GUAN YEOH, Khay
• WAI KEONG WONG
• ZHU, Yi-Jun
• FUTREAL, P. Andrew
• PANG, Brendan
• SHEN LI ZHANG
• YIJUN RUAN
• HILLMER, Axel M
• BERTRAND, Denis
• NAGARAJAN, Niranjan
• ROZEN, Steve
• TEAN TEH, Bin
• TAN, Patrick
• MCPHERSON, John R
• JIONG TAO
• RAJASEGARAN, Vikneswari
• HONG LEE HENG
• NIANTAO DENG
• GAN, Anna

Titel

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

Ist Teil von

• Nature genetics, 2012-05, Vol.44 (5), p.570-574

Ort / Verlag

New York, NY: Nature Publishing Group

Erscheinungsjahr

2012

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.