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
Small cell carcinoma of the ovary, hypercalcaemic type () is a lethal and sometimes familial ovarian tumour of young women and children. We and others recently discovered that over 90% of harbour inactivating mutations in the chromatin remodelling gene with concomitant loss of its encoded protein ()...
| Autores: | , , , , , , , , , , , , , , , , , , , , |
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| Tipo de documento: | artigo |
| Data de publicação: | 2015 |
| País: | España |
| Recursos: | Universitat Autònoma de Barcelona |
| Repositório: | Dipòsit Digital de Documents de la UAB |
| Idioma: | inglês |
| OAI Identifier: | oai:ddd.uab.cat:185416 |
| Acesso em linha: | https://ddd.uab.cat/record/185416 https://dx.doi.org/urn:doi:10.1002/path.4633 |
| Access Level: | Acceso aberto |
| Palavra-chave: | Small cell carcinoma Hypercalcaemic type Rhabdoid tumour SMARCA4/BRG1 SMARCA2/BRM SMARCB1/INI1 SWI/SNF HDAC inhibitor Inhibitor Trichostatin A Epigenetic silencing |
| Resumo: | Small cell carcinoma of the ovary, hypercalcaemic type () is a lethal and sometimes familial ovarian tumour of young women and children. We and others recently discovered that over 90% of harbour inactivating mutations in the chromatin remodelling gene with concomitant loss of its encoded protein (), one of two mutually exclusive of the / chromatin remodelling complex. To determine the specificity of loss for , we examined the expression of 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 in endometrial stromal sarcomas (4 of 52, 8%) and high-grade endometrioid carcinomas (2 of 338, 1%). Recent studies have shown that (), the other mutually exclusive of the / complex, is necessary for survival of tumour cells lacking . Therefore, we examined expression and discovered that all -negative also lacked protein by , including the cell lines and . Among ovarian tumours, the / dual loss phenotype appears completely specific for . loss was not due to mutation but rather from an absence of expression, which was restored by treatment with the histone deacetylase inhibitor trichostatin A. Re-expression of or inhibited the growth of and cell lines. Our results indicate that loss, either alone or with , is highly sensitive and specific for and that restoration of either / can inhibit the growth of cell lines. © 2015 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. |
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