Exome sequencing of serous endometrial tumors identifies recurrent somatic mutations in chromatin-remodeling and ubiquitin ligase complex genes
M Le Gallo, AJ O'Hara, ML Rudd, ME Urick… - Nature …, 2012 - nature.com
Nature genetics, 2012•nature.com
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 …
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 …
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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