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Accordingly, few studies have addressed the mechanisms of missense mutation occurrence and its functional advantage over HOM in bladder cancer development. Organoids derived from Krt5-expressing mouse urothelium (K5-mUrorganoid) demonstrated the crucial role of\n                    <jats:italic>Pten<\/jats:italic>\n                    loss in driving loss of wild-type allele of\n                    <jats:italic>Trp53<\/jats:italic>\n                    (\n                    <jats:italic>Trp53<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>R172H\/LOH<\/jats:italic>\n                    <\/jats:sup>\n                    ), which conferred tumorigenic ability to K5-mUrorganoid in athymic mice. These tumors recapitulated the histological and genetic characteristics of the human basal-squamous subtype bladder cancer. Both\n                    <jats:italic>Trp53<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>R172H\/\u0394<\/jats:italic>\n                    <\/jats:sup>\n                    <jats:italic>; Pten<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u0394\/\u0394<\/jats:italic>\n                    <\/jats:sup>\n                    and\n                    <jats:italic>Trp53<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u0394\/\u0394<\/jats:italic>\n                    <\/jats:sup>\n                    <jats:italic>; Pten<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u0394\/\u0394<\/jats:italic>\n                    <\/jats:sup>\n                    K5-mUrorganoids formed tumors in athymic mice, whereas only\n                    <jats:italic>Trp53<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>R172H\/\u0394<\/jats:italic>\n                    <\/jats:sup>\n                    <jats:italic>; Pten<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u0394\/\u0394<\/jats:italic>\n                    <\/jats:sup>\n                    K5-mUrorganoid formed tumors even when directly inoculated in immunocompetent syngeneic mice. The absence of wild-type\n                    <jats:italic>Trp53<\/jats:italic>\n                    was associated with upregulation of proliferative signaling, and the presence of a mutant\n                    <jats:italic>Trp53<\/jats:italic>\n                    allele was associated with immune-excluded microenvironment. This study highlights the functional significance of\n                    <jats:italic>p53<\/jats:italic>\n                    mutant LOH in bladder carcinogenesis conferring several hallmarks of cancer such as sustaining proliferative signaling and avoiding immune destruction, thus provides a novel immunocompetent mouse model of urothelial carcinoma harboring\n                    <jats:italic>p53<\/jats:italic>\n                    mutations as a novel tool for cancer immunology research.\n                  <\/jats:p>","DOI":"10.1038\/s41388-025-03311-5","type":"journal-article","created":{"date-parts":[[2025,2,22]],"date-time":"2025-02-22T07:42:56Z","timestamp":1740210176000},"page":"1336-1349","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["PTEN loss drives p53 LOH and immune evasion in a novel urothelial organoid model harboring p53 missense mutations"],"prefix":"10.1038","volume":"44","author":[{"given":"Akihiro","family":"Hamada","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Kita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toru","family":"Sakatani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0135-7821","authenticated-orcid":false,"given":"Kenji","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideaki","family":"Takada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryosuke","family":"Ikeuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuhei","family":"Koike","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norihiko","family":"Masuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaoru","family":"Murakami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Sano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takayuki","family":"Goto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryoichi","family":"Saito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Teramoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masakazu","family":"Fujimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narumi","family":"Hatano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mayumi","family":"Kamada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Ogawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1069-2816","authenticated-orcid":false,"given":"Takashi","family":"Kobayashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,2,22]]},"reference":[{"key":"3311_CR1","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1016\/j.eururo.2023.03.029","volume":"84","author":"I Jubber","year":"2023","unstructured":"Jubber I, Ong S, Bukavina L, Black PC, Comp\u00e9rat E, Kamat AM, et al. 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