<i>TERT</i> Promoter Mutation as a Potential Predictive Biomarker in BCG-Treated Bladder Cancer Patients
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−G...
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doaj-cb012c5aefc744c68740a8b027c8a5ee2020-11-25T02:21:13ZengMDPI AGInternational Journal of Molecular Sciences1422-00672020-01-0121394710.3390/ijms21030947ijms21030947<i>TERT</i> Promoter Mutation as a Potential Predictive Biomarker in BCG-Treated Bladder Cancer PatientsRui Batista0Luís Lima1João Vinagre2Vasco Pinto3Joana Lyra4Valdemar Máximo5Lúcio Santos6Paula Soares7Instituto de Investigação e Inovação em Saúde (i3S), 4200-135 Porto, PortugalGrupo de Patologia e Terapêutica Experimental, Instituto Português de Oncologia do Porto FG, EPE (IPO-Porto), 4200-072 Porto, PortugalInstituto de Investigação e Inovação em Saúde (i3S), 4200-135 Porto, PortugalInstituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), 4200-135 Porto, PortugalInstituto de Patologia e Imunologia Molecular da Universidade do Porto (IPATIMUP), 4200-135 Porto, PortugalInstituto de Investigação e Inovação em Saúde (i3S), 4200-135 Porto, PortugalGrupo de Patologia e Terapêutica Experimental, Instituto Português de Oncologia do Porto FG, EPE (IPO-Porto), 4200-072 Porto, PortugalInstituto de Investigação e Inovação em Saúde (i3S), 4200-135 Porto, PortugalTelomerase 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−Guérin (BCG) intravesical therapy. Methods — 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 — <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>A <i>TERTp</i> mutation was an independent predictor of nonrecurrence after BCG therapy (hazard ratio—0.382; 95% confidence interval—0.150−0.971, <i>p</i> = 0.048). Conclusions — <i>TERTp</i> 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.https://www.mdpi.com/1422-0067/21/3/947<i>tert</i> promoter mutations<i>fgfr3</i>non muscle invasive bladder cancerbcg therapy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Rui Batista Luís Lima João Vinagre Vasco Pinto Joana Lyra Valdemar Máximo Lúcio Santos Paula Soares |
spellingShingle |
Rui Batista Luís Lima João Vinagre Vasco Pinto Joana Lyra Valdemar Máximo Lúcio Santos Paula Soares <i>TERT</i> Promoter Mutation as a Potential Predictive Biomarker in BCG-Treated Bladder Cancer Patients International Journal of Molecular Sciences <i>tert</i> promoter mutations <i>fgfr3</i> non muscle invasive bladder cancer bcg therapy |
author_facet |
Rui Batista Luís Lima João Vinagre Vasco Pinto Joana Lyra Valdemar Máximo Lúcio Santos Paula Soares |
author_sort |
Rui Batista |
title |
<i>TERT</i> Promoter Mutation as a Potential Predictive Biomarker in BCG-Treated Bladder Cancer Patients |
title_short |
<i>TERT</i> Promoter Mutation as a Potential Predictive Biomarker in BCG-Treated Bladder Cancer Patients |
title_full |
<i>TERT</i> Promoter Mutation as a Potential Predictive Biomarker in BCG-Treated Bladder Cancer Patients |
title_fullStr |
<i>TERT</i> Promoter Mutation as a Potential Predictive Biomarker in BCG-Treated Bladder Cancer Patients |
title_full_unstemmed |
<i>TERT</i> Promoter Mutation as a Potential Predictive Biomarker in BCG-Treated Bladder Cancer Patients |
title_sort |
<i>tert</i> promoter mutation as a potential predictive biomarker in bcg-treated bladder cancer patients |
publisher |
MDPI AG |
series |
International Journal of Molecular Sciences |
issn |
1422-0067 |
publishDate |
2020-01-01 |
description |
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−Guérin (BCG) intravesical therapy. Methods — 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 — <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>A <i>TERTp</i> mutation was an independent predictor of nonrecurrence after BCG therapy (hazard ratio—0.382; 95% confidence interval—0.150−0.971, <i>p</i> = 0.048). Conclusions — <i>TERTp</i> 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. |
topic |
<i>tert</i> promoter mutations <i>fgfr3</i> non muscle invasive bladder cancer bcg therapy |
url |
https://www.mdpi.com/1422-0067/21/3/947 |
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