1. Exome sequencing of serous endometrial tumors identifies recurrent somatic mutations in chromatin-remodeling and ubiquitin ligase complex genes
- Author
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Suiyuan Zhang, Andrea J. O'Hara, Philip Hieter, Maria J. Merino, Meghan L. Rudd, Jessica C. Price, Nancy F. Hansen, Matthieu Le Gallo, Dennis C. Sgroi, James C. Mullikin, Mary Ellen Urick, Nigel J. O'Neil, Bryant M England, Andrew K. Godwin, and Daphne W. Bell
- Subjects
F-Box-WD Repeat-Containing Protein 7 ,Receptors, Drug ,Cell Cycle Proteins ,Sulfonylurea Receptors ,Autoantigens ,0302 clinical medicine ,Gene Frequency ,Exome ,Exome sequencing ,0303 health sciences ,Nuclear Proteins ,Ubiquitin-Protein Ligase Complexes ,3. Good health ,DNA-Binding Proteins ,Serous fluid ,030220 oncology & carcinogenesis ,Ubiquitin ligase complex ,Female ,Carcinoma, Endometrioid ,Mi-2 Nucleosome Remodeling and Deacetylase Complex ,Adult ,Ubiquitin-Protein Ligases ,Molecular Sequence Data ,Biology ,MAP Kinase Kinase Kinase 4 ,Article ,03 medical and health sciences ,Germline mutation ,Genetics ,medicine ,Humans ,Potassium Channels, Inwardly Rectifying ,EP300 ,030304 developmental biology ,Base Sequence ,Endometrial cancer ,F-Box Proteins ,Cancer ,Sequence Analysis, DNA ,medicine.disease ,Chromatin Assembly and Disassembly ,Molecular biology ,Endometrial Neoplasms ,Repressor Proteins ,Mutation ,Cancer research ,ATP-Binding Cassette Transporters ,E1A-Associated p300 Protein ,Adenocarcinoma, Clear Cell ,Transcription Factors - Abstract
Endometrial cancer is the 6th most commonly diagnosed cancer among women worldwide, causing ~74,000 deaths annually 1. Serous endometrial cancers are a clinically aggressive subtype with a poorly defined genetic etiology 2-4. We used whole exome sequencing (WES) to comprehensively search for somatic mutations within ~22,000 protein-encoding genes among 13 primary serous endometrial tumors. We subsequently resequenced 18 genes that were mutated in more than one tumor, and/or were genes that formed 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 mutated a chromatin-remodeling gene and 35% had mutated a ubiquitin ligase complex gene, implicating the frequent mutational disruption of these processes in the molecular pathogenesis of one of the deadliest forms of endometrial cancer.
- Published
- 2012