{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T14:46:13Z","timestamp":1787237173740,"version":"build-2736575974"},"reference-count":46,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,7,21]],"date-time":"2021-07-21T00:00:00Z","timestamp":1626825600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100007434","name":"Suzuken Memorial Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007434","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["19K09816"],"award-info":[{"award-number":["19K09816"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["18K16823"],"award-info":[{"award-number":["18K16823"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["17K19624"],"award-info":[{"award-number":["17K19624"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Genetically engineered mice have been the gold standard in modeling tumor development. Recent studies have demonstrated that genetically engineered organoids can develop subcutaneous tumors in immunocompromised mice, at least for organs that prefer predominant driver mutations for tumorigenesis. To further substantiate this concept, the fallopian tube (FT), a major cell of origin of ovarian high\u2010grade serous carcinoma (HGSC), which almost invariably carries\n                    <jats:italic>TP53<\/jats:italic>\n                    mutations, was investigated for p53 inactivation\u2010driven tumorigenesis. Murine FT organoids subjected to lentiviral\n                    <jats:italic>Cre<\/jats:italic>\n                    \u2010mediated\n                    <jats:italic>Trp53<\/jats:italic>\n                    deletion did not develop tumors. However, subsequent suppression of\n                    <jats:italic>Pten<\/jats:italic>\n                    and simultaneous induction of mutant\n                    <jats:italic>Pik3ca<\/jats:italic>\n                    led to the development of carcinoma\n                    <jats:italic>in situ<\/jats:italic>\n                    and HGSC\u2010like tumors, respectively, whereas concurrent deletion of\n                    <jats:italic>Apc<\/jats:italic>\n                    resulted in the development of benign cysts, mirroring frequent activation of the PI3K\/AKT axis and the marginal impact of Wnt pathway activation in HGSC. Consistent with the frequent activation of the RAS pathway in HGSC, mutant\n                    <jats:italic>Kras<\/jats:italic>\n                    cooperated with\n                    <jats:italic>Trp53<\/jats:italic>\n                    deletion for the development of tumors, which unexpectedly contained sarcoma cells in addition to carcinoma cells, despite the epithelial origin of the inoculated organoids. This finding is in sharp contrast with the exclusive adenocarcinoma development from gastrointestinal organoids with the same genotype reported in previous studies, suggesting a tissue\u2010specific epithelial\u2013mesenchymal transition program. In tumor\u2010derived organoids, the\n                    <jats:italic>Cre<\/jats:italic>\n                    \u2010mediated recombination rate reached 100% for\n                    <jats:italic>Trp53<\/jats:italic>\n                    but not for the other genes, highlighting the advantage of p53 inactivation in FT tumorigenesis. The\n                    <jats:italic>Trp53<\/jats:italic>\n                    wildtype FT organoids expressing the mutant\n                    <jats:italic>Kras<\/jats:italic>\n                    developed sarcoma and carcinoma upon\n                    <jats:italic>Cdkn2a<\/jats:italic>\n                    suppression and\n                    <jats:italic>Tgfbr2<\/jats:italic>\n                    deletion, respectively, revealing novel pro\u2010tumorigenic genetic cooperation and critical roles of TGF\u2010\u03b2 signaling for epithelial\u2013mesenchymal transition in FT\u2010derived tumorigenesis. Collectively, the organoid\u2010based approach represents a shortcut to tumorigenesis and provides novel insights into the relationships among genotype, cell type, and tumor phenotype underlying tumorigenesis. \u00a9 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.\n                  <\/jats:p>","DOI":"10.1002\/path.5752","type":"journal-article","created":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T06:39:04Z","timestamp":1624948744000},"page":"177-189","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Probing the tumorigenic potential of genetic interactions reconstituted in murine fallopian tube organoids"],"prefix":"10.1002","volume":"255","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4760-8454","authenticated-orcid":false,"given":"Yoshiaki","family":"Maru","sequence":"first","affiliation":[{"name":"Department of Molecular Carcinogenesis Chiba Cancer Center Research Institute  Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naotake","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Gynecology Chiba Cancer Center  Chiba 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