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Mutations in specific SWI\/SNF complex members are characteristic of rare chemoresistant ovarian cancer histopathological subtypes. Somatic mutations in ARID1A, encoding one of the mutually exclusive DNA-binding subunits of SWI\/SNF, occur in 42\u201367% of ovarian clear cell carcinomas (OCCC). The concomitant somatic or germline mutation and epigenetic silencing of the mutually exclusive ATPase subunits SMARCA4 and SMARCA2, respectively, occurs in Small cell carcinoma of the ovary, hypercalcaemic type (SCCOHT), with SMARCA4 mutation reported in 69\u2013100% of SCCOHT cases and SMARCA2 silencing seen 86\u2013100% of the time. Somatic ARID1A mutations also occur in endometrioid ovarian cancer (EnOC), as well as in the chronic benign condition endometriosis, possibly as precursors to the development of the endometriosis-associated cancers OCCC and EnOC. Mutation of the ARID1A paralogue ARID1B can also occur in both OCCC and SCCOHT. Mutations in other SWI\/SNF complex members, including SMARCA2, SMARCB1 and SMARCC1, occur rarely in either OCCC or SCCOHT. Abrogated SWI\/SNF raises opportunities for pharmacological inhibition, including the use of DNA damage repair inhibitors, kinase and epigenetic inhibitors, as well as immune checkpoint blockade.<\/jats:p>","DOI":"10.3390\/cancers16173068","type":"journal-article","created":{"date-parts":[[2024,9,3]],"date-time":"2024-09-03T09:56:42Z","timestamp":1725357402000},"page":"3068","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Aberrant SWI\/SNF Complex Members Are Predominant in Rare Ovarian Malignancies\u2014Therapeutic Vulnerabilities in Treatment-Resistant Subtypes"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1107-7789","authenticated-orcid":false,"given":"Yue","family":"Ma","sequence":"first","affiliation":[{"name":"Translational Oncology Group, School of Life Sciences, Faculty of Science, University of Technology Sydney, Ultimo, NSW 2007, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6724-6360","authenticated-orcid":false,"given":"Natisha R.","family":"Field","sequence":"additional","affiliation":[{"name":"Translational Oncology Group, School of Life Sciences, Faculty of Science, University of Technology Sydney, Ultimo, NSW 2007, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0580-6877","authenticated-orcid":false,"given":"Tao","family":"Xie","sequence":"additional","affiliation":[{"name":"Translational Oncology Group, School of Life Sciences, Faculty of Science, University of Technology Sydney, Ultimo, NSW 2007, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarina","family":"Briscas","sequence":"additional","affiliation":[{"name":"Translational Oncology Group, School of Life Sciences, Faculty of Science, University of Technology Sydney, Ultimo, NSW 2007, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily G.","family":"Kokinogoulis","sequence":"additional","affiliation":[{"name":"Translational Oncology Group, School of Life Sciences, Faculty of Science, University of Technology Sydney, Ultimo, NSW 2007, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6313-761X","authenticated-orcid":false,"given":"Tali S.","family":"Skipper","sequence":"additional","affiliation":[{"name":"Translational Oncology Group, School of Life Sciences, Faculty of Science, University of Technology Sydney, Ultimo, NSW 2007, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2308-0256","authenticated-orcid":false,"given":"Amani","family":"Alghalayini","sequence":"additional","affiliation":[{"name":"Translational Oncology Group, School of Life Sciences, Faculty of Science, University of Technology Sydney, Ultimo, NSW 2007, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-0990-1796","authenticated-orcid":false,"given":"Farhana A.","family":"Sarker","sequence":"additional","affiliation":[{"name":"Translational Oncology Group, School of Life Sciences, Faculty of Science, University of Technology Sydney, Ultimo, NSW 2007, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nham","family":"Tran","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering, Faculty of Engineering and IT, University of Technology Sydney, Ultimo, NSW 2007, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6047-1694","authenticated-orcid":false,"given":"Nikola A.","family":"Bowden","sequence":"additional","affiliation":[{"name":"Drug Repurposing and Medicines Research Program, Hunter Medical Research Institute, Newcastle, NSW 2289, Australia"},{"name":"School of Medicine and Public Health, University of Newcastle, Newcastle, NSW 2289, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7307-8982","authenticated-orcid":false,"given":"Kristie-Ann","family":"Dickson","sequence":"additional","affiliation":[{"name":"Translational Oncology Group, School of Life Sciences, Faculty of Science, University of Technology Sydney, Ultimo, NSW 2007, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5899-4931","authenticated-orcid":false,"given":"Deborah J.","family":"Marsh","sequence":"additional","affiliation":[{"name":"Translational Oncology Group, School of Life Sciences, Faculty of Science, University of Technology Sydney, Ultimo, NSW 2007, 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