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TERT C228T mutation in non-malignant bladder urothelium is associated with intravesical recurrence for patients with non-muscle invasive bladder cancer. | LitMetric

AI Article Synopsis

  • TERT promoter mutations, particularly C228T and C250T, are commonly found in tumors and urine of patients with urothelial carcinoma (UC) and can also appear in urine of those without cancer, indicating a potential risk for developing UC.
  • A study analyzed genomic DNA from 53 primary tumors and 428 bladder biopsy specimens of 54 patients with non-muscle-invasive bladder cancer (NMIBC), using droplet digital PCR methods to detect these mutations.
  • The findings showed that the TERT C228T mutation in nonmalignant urothelium was significantly linked to an increased risk of bladder recurrence, making it a valuable prognostic factor for monitoring NMIBC progression.

Article Abstract

Telomerase reverse transcriptase (TERT) promoter mutations are frequently found in tumors or urine from patients with urothelial carcinoma (UC). TERT promoter mutations are also detected in urine from patients with no evidence of cancer but are associated with subsequent UC development. Mutations in the TERT 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-of-concept study, we investigated the clinical utility of TERT promoter mutation analysis in NMU of patients with non-muscle-invasive bladder cancer (NMIBC). This single-institute 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 TERT C228T and C250T mutations using droplet digital PCR (ddPCR). The association between TERT promoter mutation of NMU and bladder recurrence was examined by the Kaplan-Meier method and Cox proportional hazards model. Of the 54 patients, 16 (29.6%) had a TERT C228T mutation and three (5.6%) had a TERT C250T mutation in NMU. Of 428 biopsy specimens, the TERT 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 in situ (CIS), and 58% (18/31) of CIS. During follow-up (median: 3.7 years), 22 (40.7%) patients experienced bladder recurrence and five (9.3%) experienced disease progression. Cox proportional hazard analysis showed that TERT C228T mutation in NMU was significantly associated with bladder recurrence after adjustment for cofounding factors (P = 0.0128). Thus, TERT C228T mutation was detected in NMU, which was a reliable independent prognostic factor of bladder tumor recurrence.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7530786PMC
http://dx.doi.org/10.1002/1878-0261.12746DOI Listing

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