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We previously showed that ID8, a widely-used syngeneic model of ovarian cancer, lacked any of the frequent mutations in HGSC, and used CRISPR\/Cas9 gene editing to generate derivatives with deletions in <jats:italic>Trp53<\/jats:italic> and <jats:italic>Brca2<\/jats:italic>. Here we have used one ID8 <jats:italic>Trp53<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> clone to generate further mutants, with additional mutations in <jats:italic>Brca1<\/jats:italic>, <jats:italic>Pten<\/jats:italic> and <jats:italic>Nf1<\/jats:italic>, all of which are frequently mutated or deleted in HGSC. We have also generated clones with triple deletions in <jats:italic>Trp53<\/jats:italic>, <jats:italic>Brca2<\/jats:italic> and <jats:italic>Pten<\/jats:italic>. We show that ID8 <jats:italic>Trp53<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>;<jats:italic>Brca1<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> and <jats:italic>Trp53<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>;<jats:italic>Brca2<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> cells have defective homologous recombination and increased sensitivity to both platinum and PARP inhibitor chemotherapy compared to <jats:italic>Trp53<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup>. By contrast, loss of <jats:italic>Pten<\/jats:italic> or <jats:italic>Nf1<\/jats:italic> increases growth rate <jats:italic>in vivo<\/jats:italic>, and reduces survival following cisplatin chemotherapy <jats:italic>in vivo<\/jats:italic>. Finally, we have also targeted <jats:italic>Trp53<\/jats:italic> in cells isolated from a previous transgenic murine fallopian tube carcinoma model, and confirmed that loss of p53 expression in this second model accelerates intraperitoneal growth. Together, these CRISPR-generated models represent a new and simple tool to investigate the biology of HGSC, and the ID8 cell lines are freely available to researchers.<\/jats:p>","DOI":"10.1038\/s41598-017-17119-1","type":"journal-article","created":{"date-parts":[[2017,11,28]],"date-time":"2017-11-28T09:15:41Z","timestamp":1511860541000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":98,"title":["CRISPR\/Cas9-derived models of ovarian high grade serous carcinoma targeting Brca1, Pten and Nf1, and correlation with platinum sensitivity"],"prefix":"10.1038","volume":"7","author":[{"given":"Josephine B.","family":"Walton","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malcolm","family":"Farquharson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Mason","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Port","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bjorn","family":"Kruspig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2511-1965","authenticated-orcid":false,"given":"Suzanne","family":"Dowson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Stevenson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5538-5468","authenticated-orcid":false,"given":"Daniel","family":"Murphy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Matzuk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaeyeon","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2257-2862","authenticated-orcid":false,"given":"Seth","family":"Coffelt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Blyth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9387-7586","authenticated-orcid":false,"given":"Iain A.","family":"McNeish","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,12,4]]},"reference":[{"key":"17119_CR1","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1002\/path.2696","volume":"221","author":"AA Ahmed","year":"2010","unstructured":"Ahmed, A. 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