Journal article

Dual loss of the SWI/SNF complex ATPases SMARCA4/BRG1 and SMARCA2/BRM is highly sensitive and specific for small cell carcinoma of the ovary, hypercalcaemic type

Anthony N Karnezis, Yemin Wang, Pilar Ramos, William PD Hendricks, Esther Oliva, Emanuela D'Angelo, Jaime Prat, Marisa R Nucci, Torsten O Nielsen, Christine Chow, Samuel Leung, Friedrich Kommoss, Stefan Kommoss, Annacarolina Silva, Brigitte M Ronnett, Joseph T Rabban, David D Bowtell, Bernard E Weissman, Jeffrey M Trent, C Blake Gilks Show all



Small cell carcinoma of the ovary, hypercalcaemic type (SCCOHT) is a lethal and sometimes familial ovarian tumour of young women and children. We and others recently discovered that over 90% of SCCOHTs harbour inactivating mutations in the chromatin remodelling gene SMARCA4 with concomitant loss of its encoded protein SMARCA4 (BRG1), one of two mutually exclusive ATPases of the SWI/SNF chromatin remodelling complex. To determine the specificity of SMARCA4 loss for SCCOHT, we examined the expression of SMARCA4 by immunohistochemistry in more than 3000 primary gynaecological tumours. Among ovarian tumours, it was only absent in clear cell carcinoma (15 of 360, 4%). In the uterus, it was absent..

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Awarded by National Institutes of Health

Awarded by Terry Fox Research Initiative New Frontiers Program in Cancer


Funding Acknowledgements

We thank the SCCOHT families and patients for their important contributions to TGen's institutional review board-approved study. We thank Drs Ralf Hass and Barbara Vanderhyden for kindly providing SCCOHT-1 and BIN67 cells, respectively. Viable frozen SCCOHT tumour cells used to establish patient-derived xenografts were obtained from Molecular Response (San Diego, CA, USA). This study was supported by grants from the National Institutes of Health (R01 CA195670-01; BEW, JMT, and DGH), the Terry Fox Research Initiative New Frontiers Program in Cancer (grant 1021; DGH), the Canadian Cancer Society Research Initiative (DGH and YW), the Terry Fox Foundation Strategic Health Research Training Program in Cancer Research at Canadian Institutes of Health Research (ANK), the Anne Rita Monahan Foundation (PR), the Marsha Rivkin Center for Ovarian Cancer Research, the Ovarian Cancer Alliance of Arizona, the Small Cell Ovarian Cancer Foundation, and philanthropic support to the TGen Foundation.