Loss of the Tumor Suppressor SMARCA4 in Small Cell Carcinoma of the Ovary, Hypercalcemic Type (SCCOHT)
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.
- Author (aut): Ramos, Pilar
- Author (aut): Kamezis, Anthony N.
- Author (aut): Hendricks, William P. D.
- Author (aut): Wang, Yemin
- Author (aut): Tembe, Waibhav
- Author (aut): Zismann, Victoria L.
- Author (aut): Legendre, Christophe
- Author (aut): Liang, Winnie S.
- Author (aut): Russell, Megan L.
- Author (aut): Craig, David W.
- Author (aut): Farley, John H.
- Author (aut): Monk, Bradley J.
- Author (aut): Anthony, Stephen P.
- Author (aut): Sekulic, Aleksandar
- Author (aut): Cunliffe, Heather E.
- Author (aut): Huntsman, David G.
- Author (aut): Trent, Jeffrey M.
- Contributor (ctb): College of Liberal Arts and Sciences