Journal Article

Exome sequencing identifies frequent mutation of ARID1A in molecular subtypes of gastric cancer

Yuen, Siu Tsan, Tsui, Wai Yin, Chu, Kent Man, Gibson, Neil W, Chan, Anthony K W, Shi, Stephanie T, Kan, Zhengyan, Ho, Siu Lun, Xu, Jiangchun, Rejto, Paul A, Mao, Mao, Leung, Suet Yi, Kan, Junsuo, Cheng, Grace H W, Law, Simon, Pocalyko, David J, Lee, Siu Po, Chan, Annie S Y, Wang, Kai, Roberts, Peter C, Chan, Tsun Leung

2011

Overview

Suet Leung, Jiangchun Xu and colleagues report exome sequencing of 22 gastric cancers. They found that genes involved in chromatin modification were commonly mutated, including ARID1A encoding an SWI/SNF chromatin-remodeling complex component that had a high rate of mutation. Gastric cancer is a heterogeneous disease with multiple environmental etiologies and alternative pathways of carcinogenesis 1 , 2 . Beyond mutations in TP53 , alterations in other genes or pathways account for only small subsets of the disease. We performed exome sequencing of 22 gastric cancer samples and identified previously unreported mutated genes and pathway alterations; in particular, we found genes involved in chromatin modification to be commonly mutated. A downstream validation study confirmed frequent inactivating mutations or protein deficiency of ARID1A , which encodes a member of the SWI-SNF chromatin remodeling family, in 83% of gastric cancers with microsatellite instability (MSI), 73% of those with Epstein-Barr virus (EBV) infection and 11% of those that were not infected with EBV and microsatellite stable (MSS). The mutation spectrum for ARID1A differs between molecular subtypes of gastric cancer, and mutation prevalence is negatively associated with mutations in TP53 . Clinically, ARID1A alterations were associated with better prognosis in a stage-independent manner. These results reveal the genomic landscape, and highlight the importance of chromatin remodeling, in the molecular taxonomy of gastric cancer.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 631/208/2489/144/68 / 631/208/514/1948 / 692/699/67/1504/1829 / Adult / Aged / Aged, 80 and over / Agriculture / Animal Genetics and Genomics / Biological and medical sciences / Biomedical and Life Sciences / Biomedicine / Cancer / Cancer Research / Carcinogenesis / Cell Cycle Proteins - genetics / Chromatin Assembly and Disassembly / Confidence intervals / DNA sequencing / Epstein-Barr virus / Exome / Female / Fundamental and applied biological sciences. Psychology / Gastroenterology. Liver. Pancreas. Abdomen / Gene expression / Gene Function / Gene mutations / Genes, Neoplasm / Genetic aspects / Genetic Association Studies / Genetics of eukaryotes. Biological and molecular evolution / Genomes / Health aspects / Human Genetics / Humans / Intercellular Junctions / letter / Male / Medical sciences / Microsatellite Instability / Middle Aged / Mutation / Neoplasm Staging / Nuclear Proteins - genetics / Nucleotide sequencing / Prognosis / Risk factors / Sequence Analysis, DNA / Signal Transduction / Stomach cancer / Stomach Neoplasms - diagnosis / Stomach Neoplasms - genetics / Stomach Neoplasms - mortality / Stomach. Duodenum. Small intestine. Colon. Rectum. Anus / Transcription Factors - genetics / Tumors / Validation studies / Young Adult