Abstract
Telomerase reverse transcriptase gene promoter (TERTp) mutations are recognized as one of the most frequent genetic events in bladder cancer (BC). No studies have focused on the relevance of TERTp mutations in the specific group of tumors treated with Bacillus Calmette–Guérin (BCG) intravesical therapy. Methods — 125 non muscle invasive BC treated with BCG therapy (BCG-NMIBC) were screened for TERTp mutations, TERT rs2853669 single nucleotide polymorphism, and Fibroblast Growth Factor Receptor 3 (FGFR3) hotspot mutations. Results — TERTp mutations were found in 56.0% of BCG-NMIBC and were not associated with tumor stage or grade. FGFR3 mutations were found in 44.9% of the cases and were not associated with tumor stage or grade nor with TERTp mutations. The TERT rs2853669 single nucleotide polymorphism was associated with tumors of higher grade. The specific c.1-146G>A TERTp mutation was an independent predictor of nonrecurrence after BCG therapy (hazard ratio—0.382; 95% confidence interval—0.150–0.971, p = 0.048). Conclusions — TERTp mutations are frequent in BCG-NMIBC and -146G>A appears to be an independent predictive marker of response to BCG treatment with an impact in recurrence-free survival.
Highlights
Bladder cancer (BC) ranks as the fifth most common cancer in western society and the sixth most prevalent in the world, with an increasing incidence in the past years [1]
In the 125 Bacillus Calmette–Guérin (BCG)-treated NMI bladder cancer (NMIBC) (BCG-NMIBC) tumors screened for Telomerase reverse transcriptase gene promoter (TERTp) mutations, 56.0% (70/125) of the cases were mutated
A comparison between TERTp mutation status and Fibroblast Growth Factor Receptor 3 (FGFR3) status revealed no significant association between the two genetic events in the BCG-non muscle invasive (NMI) tumors
Summary
Bladder cancer (BC) ranks as the fifth most common cancer in western society and the sixth most prevalent in the world, with an increasing incidence in the past years [1]. NMI bladder cancer (NMIBC) accounts for 70% to 80% of all BC and is present as superficial and recurrent lesions that only seldom progress to an MI phenotype. 30% to 40% of patients present either intolerance or recurrence following BCG treatment, demanding a life-long follow-up and repeated courses of treatment [24] This clinical relevance is recognized and there is a shortage of dedicated genetic markers predicting BCG-NMIBC subgroup outcomes, in particular, the recognized two most common genetic events in NMIBC—TERT promoter and FGFR3 mutations. To investigate the significance of TERTp mutations in the BCG-treated tumor response, we compared the obtained results with the available clinicopathological data, including recurrence-free survival following BCG therapy
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