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Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT), is a rare and understudied cancer with a dismal prognosis. SCCOHT's infrequency has hindered empirical study of its biology and clinical management. However, we and others have recently identified inactivating mutations in the SWI/SNF chromatin remodeling gene SMARCA4 with concomitant loss

Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT), is a rare and understudied cancer with a dismal prognosis. SCCOHT's infrequency has hindered empirical study of its biology and clinical management. However, we and others have recently identified inactivating mutations in the SWI/SNF chromatin remodeling gene SMARCA4 with concomitant loss of SMARCA4 protein in the majority of SCCOHT tumors. Here we summarize these findings and report SMARCA4 status by targeted sequencing and/or immunohistochemistry (IHC) in an additional 12 SCCOHT tumors, 3 matched germlines, and the cell line SCCOHT-1. We also report the identification of a homozygous inactivating mutation in the gene SMARCB1 in one SCCOHT tumor with wild-type SMARCA4, suggesting that SMARCB1 inactivation may also play a role in the pathogenesis of SCCOHT. To date, SMARCA4 mutations and protein loss have been reported in the majority of 69 SCCOHT cases (including 2 cell lines). These data firmly establish SMARCA4 as a tumor suppressor whose loss promotes the development of SCCOHT, setting the stage for rapid advancement in the biological understanding, diagnosis, and treatment of this rare tumor type.

ContributorsRamos, Pilar (Author) / Kamezis, Anthony N. (Author) / Hendricks, William P. D. (Author) / Wang, Yemin (Author) / Tembe, Waibhav (Author) / Zismann, Victoria L. (Author) / Legendre, Christophe (Author) / Liang, Winnie S. (Author) / Russell, Megan L. (Author) / Craig, David W. (Author) / Farley, John H. (Author) / Monk, Bradley J. (Author) / Anthony, Stephen P. (Author) / Sekulic, Aleksandar (Author) / Cunliffe, Heather E. (Author) / Huntsman, David G. (Author) / Trent, Jeffrey M. (Author) / College of Liberal Arts and Sciences (Contributor)
Created2014-11-03