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

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NIH Intramural Sequencing Center (NISC) Comparative Sequencing Program, Le Gallo, Matthieu, O'Hara, Andrea J, Rudd, Meghan L, Urick, Mary Ellen, Hansen, Nancy F, O'Neil, Nigel J, Price, Jessica C, Zhang, Suiyuan, England, Bryant M, Godwin, Andrew K, Sgroi, Dennis C, Hieter, Philip, Mullikin, James C, Merino, Maria J, Bell, Daphne W·2012·Nature Genetics

DOI 10.1038/ng.2455

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Abstract

Endometrial cancer is the sixth most commonly diagnosed cancer in women worldwide, causing ∼74,000 deaths annually. Serous endometrial cancers are a clinically aggressive subtype with a poorly defined genetic etiology. 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.

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Authors: NIH Intramural Sequencing Center (NISC) Comparative Sequencing Program, Le Gallo, M., O'Hara, A. J., Rudd, M. L., Urick, M. E., Hansen, N. F., O'Neil, N. J., Price, J. C., Zhang, S., England, B. M., Godwin, A. K., Sgroi, D. C., Hieter, P., Mullikin, J. C., Merino, M. J., & Bell, D. W.
Venue: Nature Genetics
Publisher: Springer Science and Business Media LLC
Published: 2012-10-28
Volume: 44
Issue: 12
Pages: 1310-1315
ISSN: 1061-4036 (ISSN-L)
1546-1718
DOI: 10.1038/ng.2455
OpenAlex: W2028878627
Cited by: 419
References: 61
FWCI: 15.68
Type: journal article
Language: en
Open access: green

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

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