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
Karnezis, Anthony N. (University of British Columbia. Department of Pathology and Laboratory Medicine)
Wang, Yemin (University of British Columbia. Department of Pathology and Laboratory Medicine)
Ramos, Pilar (Translational Genomics Research Institute)
Hendricks, William P. D. (Translational Genomics Research Institute)
Oliva, Esther (Massachusetts General Hospital (Boston))
D'Angelo, Emanuela (Institut d'Investigació Biomèdica Sant Pau)
Prat, Jaime (Institut d'Investigació Biomèdica Sant Pau)
Nucci, Marisa R. (Brigham and Women's Hospital (Boston, Estats Units d'Amèrica))
Nielsen, Torsten O. (University of British Columbia. Department of Pathology and Laboratory Medicine)
Chow, Christine (University of British Columbia. Genetic Pathology Evaluation Centre)
Leung, Samuel (University of British Columbia. Genetic Pathology Evaluation Centre)
Kommoss, Friedrich (Synlab MVZ Pathologie)
Kommoss, Stefan (University Hospital of Tübingen (Alemanya))
Silva, Annacarolina (Harvard Medical School. The James Homer Wright Pathology Laboratories)
Ronnett, Brigitte M. (The Johns Hopkins Hospital. Department of Pathology)
Rabban, Joseph T. (University of California San Francisco. Department of Anatomic Pathology)
Bowtell, David D. (Peter MacCallum Cancer Centre)
Weissman, Bernard E. (University of North Carolina. Department of Pathology and Laboratory Medicine)
Trent, Jeffrey M. (Translational Genomics Research Institute)
Gilks, C. Blake (University of British Columbia. Department of Pathology and Laboratory Medicine)
Huntsman, David G. (University of British Columbia. Department of Pathology and Laboratory Medicine)
Universitat Autònoma de Barcelona

Fecha:	2015
Resumen:	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.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Small cell carcinoma ; Hypercalcaemic type ; Rhabdoid tumour ; SMARCA4/BRG1 ; SMARCA2/BRM ; SMARCB1/INI1 ; SWI/SNF ; HDAC inhibitor ; Inhibitor ; Trichostatin A ; Epigenetic silencing
Publicado en:	The Journal of Pathology, Vol. 238, Issue 3 (december 2015) , p. 389-400, ISSN 1096-9896

DOI: 10.1002/path.4633
PMID: 26356327

12 p, 3.2 MB

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