{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:05:57Z","timestamp":1792782357787,"version":"4.5.0"},"reference-count":28,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,7,25]],"date-time":"2017-07-25T00:00:00Z","timestamp":1500940800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"National Cancer Institute of the National Institutes of Health","award":["P30CA046592"],"award-info":[{"award-number":["P30CA046592"]}]},{"name":"National Cancer Institute of the National Institutes of Health","award":["R01CA188516"],"award-info":[{"award-number":["R01CA188516"]}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2017,9]]},"abstract":"Abstract<\/jats:title>\n \n Recent studies have suggested that the most common and lethal type of \u2018ovarian\u2019 cancer, i.e. high\u2010grade serous carcinoma (HGSC), usually arises from epithelium on the fallopian tube fimbriae, and not from the ovarian surface epithelium. We have developed\n Ovgp1\u2010iCreER<\/jats:italic>\n \n T2<\/jats:italic>\n <\/jats:sup>\n mice in which the\n Ovgp1<\/jats:italic>\n promoter controls expression of tamoxifen\u2010regulated Cre recombinase in oviductal epithelium\u00a0\u2013\u00a0the murine equivalent of human fallopian tube epithelium (FTE). We employed\n Ovgp1\u2010iCreER<\/jats:italic>\n \n T2<\/jats:italic>\n <\/jats:sup>\n mice to show that FTE\u2010specific inactivation of several different combinations of tumour suppressor genes that are recurrently mutated in human HGSCs\u00a0\u2013\u00a0namely\n Brca1<\/jats:italic>\n ,\n Trp53<\/jats:italic>\n ,\n Rb1<\/jats:italic>\n , and\n Nf1<\/jats:italic>\n \u00a0\u2013\u00a0results in serous tubal intraepithelial carcinomas (STICs) that progress to HGSC or carcinosarcoma, and to widespread metastatic disease in a subset of mice. The cancer phenotype is highly penetrant and more rapid in mice carrying engineered alleles of all four tumour suppressor genes.\n Brca1<\/jats:italic>\n ,\n Trp53<\/jats:italic>\n and\n Pten<\/jats:italic>\n inactivation in the oviduct also results in STICs and HGSCs, and is associated with diffuse epithelial hyperplasia and mucinous metaplasia, which are not observed in mice with intact\n Pten<\/jats:italic>\n . Oviductal tumours arise earlier in these mice than in those with\n Brca1<\/jats:italic>\n ,\n Trp53<\/jats:italic>\n ,\n Rb1<\/jats:italic>\n and\n Nf1<\/jats:italic>\n inactivation. Tumour initiation and\/or progression in mice lacking conditional\n Pten<\/jats:italic>\n alleles probably require the acquisition of additional defects, a notion supported by our identification of loss of the wild\u2010type\n Rb1<\/jats:italic>\n allele in the tumours of mice carrying only one floxed\n Rb1<\/jats:italic>\n allele. Collectively, the models closely recapitulate the heterogeneity and histological, genetic and biological features of human HGSC. These models should prove useful for studying the pathobiology and genetics of HGSC\n in vivo<\/jats:italic>\n , and for testing new approaches for prevention, early detection, and treatment. Copyright \u00a9 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.\n <\/jats:p>","DOI":"10.1002\/path.4927","type":"journal-article","created":{"date-parts":[[2017,6,13]],"date-time":"2017-06-13T11:06:37Z","timestamp":1497351997000},"page":"16-25","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":94,"title":["High\u2010grade serous carcinomas arise in the mouse oviduct via defects linked to the human disease"],"prefix":"10.1002","volume":"243","author":[{"given":"Yali","family":"Zhai","sequence":"first","affiliation":[{"name":"Department of Pathology University of Michigan Medical School Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rong","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Michigan Medical School Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rork","family":"Kuick","sequence":"additional","affiliation":[{"name":"Department of Biostatistics University of Michigan School of Public Health Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael S","family":"Sessine","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Michigan Medical School Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Schulman","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Michigan Medical School Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan","family":"Green","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Michigan Medical School Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric R","family":"Fearon","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Michigan Medical School Ann Arbor MI USA"},{"name":"Department of Internal Medicine University of Michigan Medical School Ann Arbor MI USA"},{"name":"Department of Human Genetics University of Michigan Medical School Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0500-9998","authenticated-orcid":false,"given":"Kathleen R","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Michigan Medical School Ann Arbor MI USA"},{"name":"Department of Internal Medicine University of Michigan Medical School Ann Arbor MI 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