<i>TERT</i> Promoter Mutation as a Potential Predictive Biomarker in BCG-Treated Bladder Cancer Patients

• Main Authors: Rui Batista, Luís Lima, João Vinagre, Vasco Pinto, Joana Lyra, Valdemar Máximo, Lúcio Santos, Paula Soares
• Format: Article
• Language: English
• Published: MDPI AG 2020-01-01
• Series: International Journal of Molecular Sciences
• Subjects: <i>tert</i> promoter mutations; <i>fgfr3</i>; non muscle invasive bladder cancer; bcg therapy
• Online Access: https://www.mdpi.com/1422-0067/21/3/947

Telomerase reverse transcriptase gene promoter (<i>TERTp</i>) 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&#8722;Gu&#233;rin (BCG) intravesical therapy. Methods &#8212; 125 non muscle invasive BC treated with BCG therapy (BCG-NMIBC) were screened for <i>TERTp</i> mutations, <i>TERT</i> rs2853669 single nucleotide polymorphism, and Fibroblast Growth Factor Receptor 3 (<i>FGFR3</i>) hotspot mutations. Results &#8212; <i>TERTp</i> mutations were found in 56.0% of BCG-NMIBC and were not associated with tumor stage or grade. <i>FGFR3</i> mutations were found in 44.9% of the cases and were not associated with tumor stage or grade nor with <i>TERTp</i> mutations. The <i>TERT</i> rs2853669 single nucleotide polymorphism was associated with tumors of higher grade. The specific c.1-146G&gt;A <i>TERTp</i> mutation was an independent predictor of nonrecurrence after BCG therapy (hazard ratio&#8212;0.382; 95% confidence interval&#8212;0.150&#8722;0.971, <i>p</i> = 0.048). Conclusions &#8212; <i>TERTp</i> mutations are frequent in BCG-NMIBC and -146G&gt;A appears to be an independent predictive marker of response to BCG treatment with an impact in recurrence-free survival.