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.
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- Loss of the Tumor Suppressor SMARCA4 in Small Cell Carcinoma of the Ovary, Hypercalcemic Type (SCCOHT)
- Ramos, 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)
- Digital object identifier: 10.4161/2167549X.2014.967148
- Identifier TypeInternational standard serial numberIdentifier Value2167-5511
- The final version of this article, as published in Rare Diseases, can be viewed online at: http://www.tandfonline.com/doi/full/10.4161/2167549X.2014.967148
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Ramos, P., Karnezis, A. N., Hendricks, W. P., Wang, Y., Tembe, W., Zismann, V. L., . . . Trent, J. M. (2014). Loss of the tumor suppressor SMARCA4 in small cell carcinoma of the ovary, hypercalcemic type (SCCOHT). Rare Diseases, 2(1). doi:10.4161/2167549x.2014.967148