{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T11:17:12Z","timestamp":1775474232797,"version":"3.50.1"},"reference-count":33,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T00:00:00Z","timestamp":1768435200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T00:00:00Z","timestamp":1768435200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2026,5]]},"abstract":"\n Background<\/jats:title>\n Clear cell adenocarcinoma (CCA) of the urinary tract is a rare genitourinary malignancy that primarily arises in the urethra and bladder. Due to its rarity, the molecular landscape of these tumours remains poorly characterized. In this large series, we aimed to molecularly characterize CCA to gain insights into its pathogenesis and identify potential targets for therapy.<\/jats:p>\n <\/jats:sec>\n \n Design<\/jats:title>\n Formalin\u2010fixed, paraffin\u2010embedded tumour tissue blocks from 19 cases of CCA were subjected to molecular profiling using a targeted next\u2010generation sequencing (NGS) panel.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The most common alteration was a gain\u2010of\u2010function mutation in\n PIK3CA<\/jats:italic>\n (74%), followed by mutations in\n KRAS<\/jats:italic>\n (26%),\n ERBB2<\/jats:italic>\n (21%),\n SMAD4<\/jats:italic>\n (21%),\n RB1<\/jats:italic>\n (16%),\n TP53<\/jats:italic>\n (5%),\n MET<\/jats:italic>\n (5%) and\n APC<\/jats:italic>\n (5%). Thirteen tumours harboured co\u2010mutations. Five cases showed concurrent\n PIK3CA<\/jats:italic>\n and\n KRAS<\/jats:italic>\n mutations, while the remaining tumours had either isolated\n PIK3CA<\/jats:italic>\n alterations or co\u2010occurring loss\u2010of\u2010function mutations in tumour suppressor genes, including\n RB1 point<\/jats:italic>\n mutation,\n SMAD4<\/jats:italic>\n inactivation,\n APC<\/jats:italic>\n truncation or\n TP53<\/jats:italic>\n inactivation. Eight patients died of disease, with a mean follow\u2010up of 14\u2009months (range, 3\u201331\u2009months). Notably, all eight deceased patients and two of the surviving patients harboured\n PIK3CA<\/jats:italic>\n mutations.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n In summary, we identified a distinct oncogenic pathway in CCA of the urinary bladder, most commonly involving activation of the\n PI3K\/AKT\/mTOR<\/jats:italic>\n pathway through gain\u2010of\u2010function mutations in\n PIK3CA<\/jats:italic>\n (74%) and\/or\n KRAS<\/jats:italic>\n (26%).\u00a0These tumours frequently harbour loss\u2010of\u2010function mutations in tumour suppressor genes (\n TP53<\/jats:italic>\n ,\n SMAD4<\/jats:italic>\n ,\u00a0\n RB1<\/jats:italic>\n and\n APC<\/jats:italic>\n ) and point\/missense mutations of proto\u2010oncogenes (\n ERBB2<\/jats:italic>\n and\u00a0\n MET<\/jats:italic>\n ).\u00a0Our study also highlights potential\u00a0therapeutic targets for this aggressive malignancy.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/his.70096","type":"journal-article","created":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T11:20:59Z","timestamp":1768476059000},"page":"1167-1183","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Molecular characterization of clear cell adenocarcinoma of the urinary bladder"],"prefix":"10.1111","volume":"88","author":[{"given":"Shilpy","family":"Jha","sequence":"first","affiliation":[{"name":"Department of Pathology Manipal Hospitals Bangalore India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3051-8009","authenticated-orcid":false,"given":"Anandi","family":"Lobo","sequence":"additional","affiliation":[{"name":"Department of Pathology Kapoor Centre of Urology and Pathology Raipur 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