PMID- 35024637 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220716 IS - 2666-1683 (Electronic) IS - 2666-1691 (Print) IS - 2666-1683 (Linking) VI - 35 DP - 2022 Jan TI - TERT Promoter Mutations in Keratinizing and Nonkeratinizing Squamous Metaplasia of the Urinary Tract. PG - 74-78 LID - 10.1016/j.euros.2021.11.007 [doi] AB - We identified urothelial tract biopsy and resection specimens with keratinizing squamous metaplasia (KSM), nonkeratinizing squamous metaplasia (NKSM), and urothelial and squamous carcinomas over a 20-yr period, focusing on cases with neurogenic lower urinary tract dysfunction (NLUTD) and/or those with spatial or temporal variation in sampling. TERT promoter mutations as assessed via allele-specific polymerase chain reaction were surprisingly common in our testing cohort, identified not only in 15 (94%) invasive cancer foci but also in 13 (68%) examples of KSM and seven (70%) examples of NKSM. TERT promoter mutations were present in 23 foci from NLUTD specimens and 11 foci from bladder diverticula, including in foci of KSM, NKSM, and unremarkable urothelium from cases with no clinical association with previous, concurrent, or subsequent cancer. Our demonstration of temporally and spatially persistent TERT promoter mutation in examples of KSM and NKSM in cases of bladder cancer and in morphologically benign cases with neurogenic dysfunction suggests a molecular mechanism by which such pre-neoplastic lesions can potentially progress and develop into overt carcinoma. Given the interest in TERT promoter mutations as a potential biomarker for the development of bladder cancer, these findings possibly explain the association between conditions with chronic urinary bladder injury (such as the natural history of NLUTD) and higher risk of bladder cancer. TERT promoter mutations may represent an early event in bladder cancer tumorogenesis, and our findings expand on the clinical ramifications and predictive value of TERT promoter mutations in this context. PATIENT SUMMARY: Mutations in the TERT gene are the most common genetic changes in bladder cancer. We found that these mutations are also sometimes present in patients with chronic bladder irritation such as neurogenic bladder dysfunction and changes to the lining of the bladder that pathologists would consider "benign." This finding might explain why such conditions are associated with the development of bladder cancer. CI - (c) 2021 The Author(s). FAU - Taylor, Alexander S AU - Taylor AS AD - Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA. FAU - Newell, Brandon AU - Newell B AD - Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA. FAU - Chinnaiyan, Arul M AU - Chinnaiyan AM AD - Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA. AD - Department of Urology, University of Michigan Medical School, Ann Arbor, MI, USA. AD - Rogel Cancer Center, Michigan Medicine, Ann Arbor, MI, USA. AD - Michigan Center for Translational Pathology, Ann Arbor, MI, USA. AD - Howard Hughes Medical Institute, Ann Arbor, MI, USA. FAU - Hafez, Khaled S AU - Hafez KS AD - Department of Urology, University of Michigan Medical School, Ann Arbor, MI, USA. FAU - Weizer, Alon Z AU - Weizer AZ AD - Department of Urology, University of Michigan Medical School, Ann Arbor, MI, USA. FAU - Spratt, Daniel E AU - Spratt DE AD - Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, OH, USA. FAU - Cameron, Anne P AU - Cameron AP AD - Department of Urology, University of Michigan Medical School, Ann Arbor, MI, USA. FAU - Al-Ahmadie, Hikmat A AU - Al-Ahmadie HA AD - Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. FAU - Gupta, Sounak AU - Gupta S AD - Department of Pathology, Mayo Clinic, Rochester, MN, USA. FAU - Montgomery, Jeffrey S AU - Montgomery JS AD - Department of Urology, University of Michigan Medical School, Ann Arbor, MI, USA. FAU - Betz, Bryan L AU - Betz BL AD - Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA. FAU - Brown, Noah AU - Brown N AD - Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA. FAU - Mehra, Rohit AU - Mehra R AD - Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA. AD - Rogel Cancer Center, Michigan Medicine, Ann Arbor, MI, USA. AD - Michigan Center for Translational Pathology, Ann Arbor, MI, USA. LA - eng GR - P30 CA008748/CA/NCI NIH HHS/United States PT - Journal Article DEP - 20220103 PL - Netherlands TA - Eur Urol Open Sci JT - European urology open science JID - 101771568 PMC - PMC8738896 OTO - NOTNLM OT - Bladder diverticula OT - Keratinizing squamous metaplasia OT - Neurogenic bladder OT - Neurogenic lower urinary tract dysfunction OT - Nonkeratinizing squamous metaplasia OT - Squamous cell carcinoma OT - TERT OT - Urinary bladder OT - Urothelial carcinoma EDAT- 2022/01/14 06:00 MHDA- 2022/01/14 06:01 PMCR- 2022/01/03 CRDT- 2022/01/13 12:36 PHST- 2021/11/15 00:00 [accepted] PHST- 2022/01/13 12:36 [entrez] PHST- 2022/01/14 06:00 [pubmed] PHST- 2022/01/14 06:01 [medline] PHST- 2022/01/03 00:00 [pmc-release] AID - S2666-1683(21)03385-1 [pii] AID - 10.1016/j.euros.2021.11.007 [doi] PST - epublish SO - Eur Urol Open Sci. 2022 Jan 3;35:74-78. doi: 10.1016/j.euros.2021.11.007. eCollection 2022 Jan.