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.; Wang, Yemin; Ramos, Pilar; Hendricks, William P. D.; Oliva, Esther; D'Angelo, Emanuela|||0000-0002-6173-1806; Prat, Jaime|||0000-0002-9787-3304; Nucci, Marisa R.; Nielsen, Torsten O.; Chow, Christine; Leung, Samuel; Kommoss, Friedrich; Kommoss, Stefan; Silva, Annacarolina; Ronnett, Brigitte M.; Rabban, Joseph T.; Bowtell, David D.; Weissman, Bernard E.; Trent, Jeffrey M.; Gilks, C. Blake; Huntsman, David G.|||0000-0003-4934-3322

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 ()...

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Autores:	Karnezis, Anthony N., Wang, Yemin, Ramos, Pilar, Hendricks, William P. D., Oliva, Esther, D'Angelo, Emanuela\|\|\|0000-0002-6173-1806, Prat, Jaime\|\|\|0000-0002-9787-3304, Nucci, Marisa R., Nielsen, Torsten O., Chow, Christine, Leung, Samuel, Kommoss, Friedrich, Kommoss, Stefan, Silva, Annacarolina, Ronnett, Brigitte M., Rabban, Joseph T., Bowtell, David D., Weissman, Bernard E., Trent, Jeffrey M., Gilks, C. Blake, Huntsman, David G.\|\|\|0000-0003-4934-3322
Tipo de recurso:	artículo
Fecha de publicación:	2015
País:	España
Institución:	Universitat Autònoma de Barcelona
Repositorio:	Dipòsit Digital de Documents de la UAB
Idioma:	inglés
OAI Identifier:	oai:ddd.uab.cat:185416
Acceso en línea:	https://ddd.uab.cat/record/185416 https://dx.doi.org/urn:doi:10.1002/path.4633
Access Level:	acceso abierto
Palabra clave:	Small cell carcinoma Hypercalcaemic type Rhabdoid tumour SMARCA4/BRG1 SMARCA2/BRM SMARCB1/INI1 SWI/SNF HDAC inhibitor Inhibitor Trichostatin A Epigenetic silencing

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spelling	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 typeKarnezis, Anthony N.Wang, YeminRamos, PilarHendricks, William P. D.Oliva, EstherD'Angelo, Emanuela\|\|\|0000-0002-6173-1806Prat, Jaime\|\|\|0000-0002-9787-3304Nucci, Marisa R.Nielsen, Torsten O.Chow, ChristineLeung, SamuelKommoss, FriedrichKommoss, StefanSilva, AnnacarolinaRonnett, Brigitte M.Rabban, Joseph T.Bowtell, David D.Weissman, Bernard E.Trent, Jeffrey M.Gilks, C. BlakeHuntsman, David G.\|\|\|0000-0003-4934-3322Small cell carcinomaHypercalcaemic typeRhabdoid tumourSMARCA4/BRG1SMARCA2/BRMSMARCB1/INI1SWI/SNFHDAC inhibitorInhibitorTrichostatin AEpigenetic silencingSmall 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.Universitat Autònoma de Barcelona 22015-01-0120152015-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/185416https://dx.doi.org/urn:doi:10.1002/path.4633reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Aquest 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.https://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:1854162026-06-06T12:50:31Z
dc.title.none.fl_str_mv	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
title	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
spellingShingle	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. Small cell carcinoma Hypercalcaemic type Rhabdoid tumour SMARCA4/BRG1 SMARCA2/BRM SMARCB1/INI1 SWI/SNF HDAC inhibitor Inhibitor Trichostatin A Epigenetic silencing
title_short	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
title_full	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
title_fullStr	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
title_full_unstemmed	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
title_sort	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
dc.creator.none.fl_str_mv	Karnezis, Anthony N. Wang, Yemin Ramos, Pilar Hendricks, William P. D. Oliva, Esther D'Angelo, Emanuela\|\|\|0000-0002-6173-1806 Prat, Jaime\|\|\|0000-0002-9787-3304 Nucci, Marisa R. Nielsen, Torsten O. Chow, Christine Leung, Samuel Kommoss, Friedrich Kommoss, Stefan Silva, Annacarolina Ronnett, Brigitte M. Rabban, Joseph T. Bowtell, David D. Weissman, Bernard E. Trent, Jeffrey M. Gilks, C. Blake Huntsman, David G.\|\|\|0000-0003-4934-3322
author	Karnezis, Anthony N.
author_facet	Karnezis, Anthony N. Wang, Yemin Ramos, Pilar Hendricks, William P. D. Oliva, Esther D'Angelo, Emanuela\|\|\|0000-0002-6173-1806 Prat, Jaime\|\|\|0000-0002-9787-3304 Nucci, Marisa R. Nielsen, Torsten O. Chow, Christine Leung, Samuel Kommoss, Friedrich Kommoss, Stefan Silva, Annacarolina Ronnett, Brigitte M. Rabban, Joseph T. Bowtell, David D. Weissman, Bernard E. Trent, Jeffrey M. Gilks, C. Blake Huntsman, David G.\|\|\|0000-0003-4934-3322
author_role	author
author2	Wang, Yemin Ramos, Pilar Hendricks, William P. D. Oliva, Esther D'Angelo, Emanuela\|\|\|0000-0002-6173-1806 Prat, Jaime\|\|\|0000-0002-9787-3304 Nucci, Marisa R. Nielsen, Torsten O. Chow, Christine Leung, Samuel Kommoss, Friedrich Kommoss, Stefan Silva, Annacarolina Ronnett, Brigitte M. Rabban, Joseph T. Bowtell, David D. Weissman, Bernard E. Trent, Jeffrey M. Gilks, C. Blake Huntsman, David G.\|\|\|0000-0003-4934-3322
author2_role	author author author author author author author author author author author author author author author author author author author author
dc.contributor.none.fl_str_mv	Universitat Autònoma de Barcelona
dc.subject.none.fl_str_mv	Small cell carcinoma Hypercalcaemic type Rhabdoid tumour SMARCA4/BRG1 SMARCA2/BRM SMARCB1/INI1 SWI/SNF HDAC inhibitor Inhibitor Trichostatin A Epigenetic silencing
topic	Small cell carcinoma Hypercalcaemic type Rhabdoid tumour SMARCA4/BRG1 SMARCA2/BRM SMARCB1/INI1 SWI/SNF HDAC inhibitor Inhibitor Trichostatin A Epigenetic silencing
description	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.
publishDate	2015
dc.date.none.fl_str_mv	2 2015-01-01 2015 2015-01-01
dc.type.none.fl_str_mv	Article http://purl.org/coar/resource_type/c_6501 VoR http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv	info:eu-repo/semantics/article
format	article
dc.identifier.none.fl_str_mv	https://ddd.uab.cat/record/185416 https://dx.doi.org/urn:doi:10.1002/path.4633
url	https://ddd.uab.cat/record/185416 https://dx.doi.org/urn:doi:10.1002/path.4633
dc.language.none.fl_str_mv	Inglés eng
language_invalid_str_mv	Inglés
language	eng
dc.rights.none.fl_str_mv	open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/
dc.rights.openaire.fl_str_mv	info:eu-repo/semantics/openAccess
rights_invalid_str_mv	open access http://purl.org/coar/access_right/c_abf2 https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv	openAccess
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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

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