Journal Article

Exome sequencing of serous endometrial tumors identifies recurrent somatic mutations in chromatin-remodeling and ubiquitin ligase complex genes

Hieter, Philip, Merino, Maria J, Rudd, Meghan L, Hansen, Nancy F, Bell, Daphne W, Urick, Mary Ellen, Godwin, Andrew K, Sgroi, Dennis C, Price, Jessica C, England, Bryant M, Mullikin, James C, O'Hara, Andrea J, O'Neil, Nigel J, Le Gallo, Matthieu, Zhang, Suiyuan

2012

Overview

Daphne Bell and colleagues report exome sequences of serous endometrial tumors, a clinically aggressive subtype of endometrial cancer. The authors identified recurrent somatic mutations in CHD4 , EP300 , ARID1A , TSPYL2 , FBXW7 , SPOP , MAP3K4 and ABCC9 . Endometrial cancer is the sixth most commonly diagnosed cancer in women worldwide, causing ∼74,000 deaths annually 1 . Serous endometrial cancers are a clinically aggressive subtype with a poorly defined genetic etiology 2 , 3 , 4 . We used whole-exome sequencing to comprehensively search for somatic mutations within ∼22,000 protein-encoding genes in 13 primary serous endometrial tumors. We subsequently resequenced 18 genes, which were mutated in more than 1 tumor and/or were components of an enriched functional grouping, from 40 additional serous tumors. We identified high frequencies of somatic mutations in CHD4 (17%), EP300 (8%), ARID1A (6%), TSPYL2 (6%), FBXW7 (29%), SPOP (8%), MAP3K4 (6%) and ABCC9 (6%). Overall, 36.5% of serous tumors had a mutated chromatin-remodeling gene, and 35% had a mutated ubiquitin ligase complex gene, implicating frequent mutational disruption of these processes in the molecular pathogenesis of one of the deadliest forms of endometrial cancer.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: 631/208/514/1948 / 631/208/737 / 631/67/1517/1931 / Adenocarcinoma, Clear Cell - genetics / Adult / Agriculture / Animal Genetics and Genomics / ATP-Binding Cassette Transporters - genetics / Autoantigens - genetics / Base Sequence / Biological and medical sciences / Biomedicine / Cancer / Cancer Research / Carcinoma, Endometrioid - genetics / Cell Cycle Proteins - genetics / Cell physiology / Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes / Chromatin Assembly and Disassembly - genetics / Diagnosis / DNA-Binding Proteins / E1A-Associated p300 Protein - genetics / Endometrial cancer / Endometrial Neoplasms - genetics / Exome - genetics / Exome sequencing / F-Box Proteins - genetics / F-Box-WD Repeat-Containing Protein 7 / Female / Fundamental and applied biological sciences. Psychology / Gene Frequency / Gene Function / Gene mutations / Genetic aspects / Genetics / Genetics of eukaryotes. Biological and molecular evolution / Health aspects / Human Genetics / Humans / letter / MAP Kinase Kinase Kinase 4 - genetics / Medical research / Mi-2 Nucleosome Remodeling and Deacetylase Complex - genetics / Molecular and cellular biology / Molecular Sequence Data / Mutation / Nuclear Proteins - genetics / Potassium Channels, Inwardly Rectifying - genetics / Proteins / Receptors, Drug - genetics / Repressor Proteins - genetics / Sequence Analysis, DNA / Sulfonylurea Receptors / Transcription Factors - genetics / Tumors / Ubiquitin-Protein Ligase Complexes - genetics / Ubiquitin-Protein Ligases - genetics