{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T06:24:54Z","timestamp":1778912694757,"version":"3.51.4"},"reference-count":34,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2020,6,27]],"date-time":"2020-06-27T00:00:00Z","timestamp":1593216000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP 20K18139"],"award-info":[{"award-number":["JP 20K18139"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Oncology"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:p>Telomerase reverse transcriptase (<jats:italic>TERT<\/jats:italic>) promoter mutations are frequently found in tumors or urine from patients with urothelial carcinoma (UC). <jats:italic>TERT<\/jats:italic> promoter mutations are also detected in urine from patients with no evidence of cancer but are associated with subsequent UC development. Mutations in the <jats:italic>TERT<\/jats:italic> promoter are thought to be present in nonmalignant urothelium (NMU) during early stages of tumor formation prior to pathological change, but this has not been proven directly. In this proof\u2010of\u2010concept study, we investigated the clinical utility of <jats:italic>TERT<\/jats:italic> promoter mutation analysis in NMU of patients with non\u2010muscle\u2010invasive bladder cancer (NMIBC). This single\u2010institute study included 53 primary tumors and 428 systematic bladder biopsy specimens from 54 patients with NMIBC. All patients underwent systematic random biopsy and transurethral resection of the bladder tumor. Genomic DNA was analyzed for <jats:italic>TERT<\/jats:italic> C228T and C250T mutations using droplet digital PCR (ddPCR). The association between <jats:italic>TERT<\/jats:italic> promoter mutation of NMU and bladder recurrence was examined by the Kaplan\u2013Meier method and Cox proportional hazards model. Of the 54 patients, 16 (29.6%) had a <jats:italic>TERT<\/jats:italic> C228T mutation and three (5.6%) had a <jats:italic>TERT<\/jats:italic> C250T mutation in NMU. Of 428 biopsy specimens, the <jats:italic>TERT<\/jats:italic> C228T mutation was detected in 9% (31\/364) of normal urothelium, 27% (4\/15) of urothelial dysplasia (UD), 50% (9\/18) of UD suspicious for carcinoma <jats:italic>in\u00a0situ<\/jats:italic> (CIS), and 58% (18\/31) of CIS. During follow\u2010up (median: 3.7\u00a0years), 22 (40.7%) patients experienced bladder recurrence and five (9.3%) experienced disease progression. Cox proportional hazard analysis showed that <jats:italic>TERT<\/jats:italic> C228T mutation in NMU was significantly associated with bladder recurrence after adjustment for cofounding factors (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.0128). Thus, <jats:italic>TERT<\/jats:italic> C228T mutation was detected in NMU, which was a reliable independent prognostic factor of bladder tumor recurrence.<\/jats:p>","DOI":"10.1002\/1878-0261.12746","type":"journal-article","created":{"date-parts":[[2020,6,13]],"date-time":"2020-06-13T20:26:01Z","timestamp":1592079961000},"page":"2375-2383","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["<i>TERT<\/i> C228T mutation in non\u2010malignant bladder urothelium is associated with intravesical recurrence for patients with non\u2010muscle invasive bladder cancer"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4701-5635","authenticated-orcid":false,"given":"Yujiro","family":"Hayashi","sequence":"first","affiliation":[{"name":"Department of Urology Osaka University Graduate School of Medicine Suita 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