Small cell carcinoma of the ovary, hypercalcemic type, displays frequent inactivating germline and somatic mutations in SMARCA4

• DOI: 10.1038/ng.2928
• Publication Date: 2014-03-24T04:17:50Z
• Authors: Pilar Ramos; Anthony N Karnezis; David W Craig; Aleksandar Sekulic; Megan L Russell; William P D Hendr...; Jason J Corneveaux; Michael T Barrett; Karey Shumansky; Yidong Yang; Sohrab P Shah; Leah M Prentice; Marco A Marra; Jeffrey Kiefer; Victoria L Zismann; Troy A McEachron; Bodour Salhia; Jaime Prat; Emanuela D'Angelo; Blaise A Clarke; Joseph G Pressey; John H Farley; Stephen P Anthony; Richard B S Roden; Heather E Cunliffe; David G Huntsman; Jeffrey M Trent
• Keywords: Electrophoresis; DNA, Complementary; Molecular Sequence Data; Medical and Health Sciences; Rare Diseases; Complementary; Genetics; Humans; Exome; Carcinoma, Small Cell; Cancer; Gene Library; Ovarian Neoplasms; Polyacrylamide Gel; Base Sequence; Carcinoma; DNA Helicases; Chromosome Mapping; Computational Biology; Nuclear Proteins; DNA; Sequence Analysis, DNA; Small Cell; Biological Sciences; Chromatin Assembly and Disassembly; Immunohistochemistry; Ovarian Cancer; 3. Good health; Mutation; Electrophoresis, Polyacrylamide Gel; Female; Sequence Analysis; Developmental Biology; Transcription Factors

Small cell carcinoma of the ovary of hypercalcemic type (SCCOHT) is an extremely rare, aggressive cancer affecting children and young women. We identified germline and somatic inactivating mutations in the SWI/SNF chromatin-remodeling gene SMARCA4 in 75% (9/12) of SCCOHT cases in addition to SMARCA4 protein loss in 82% (14/17) of SCCOHT tumors but in only 0.4% (2/485) of other primary ovarian tumors. These data implicate SMARCA4 in SCCOHT oncogenesis.