Comprehensive behavioural assessment of TERT in bladder cancer.
Biomarker
Bladder cancer
Gene expression
Mutation
TERT promoter
THOR
Telomere length
Journal
Urologic oncology
ISSN: 1873-2496
Titre abrégé: Urol Oncol
Pays: United States
ID NLM: 9805460
Informations de publication
Date de publication:
14 Aug 2024
14 Aug 2024
Historique:
received:
11
03
2024
revised:
20
06
2024
accepted:
27
06
2024
medline:
16
8
2024
pubmed:
16
8
2024
entrez:
15
8
2024
Statut:
aheadofprint
Résumé
Telomerase activity plays a crucial role in cancer development and progression. Thus, telomerase activation through the interplay of mutations and epigenetic alterations in the telomerase reverse transcriptase (TERT) promoter may provide further insight into bladder cancer induction and progression. In this study 100 bladder tumour tissues were selected, and four molecular signatures were analysed: THOR methylation status, TERT promotor mutation, telomere length, and TERT expression. In our study, 88% of bladder cancer patients had an hypermethylation of the THOR region and 60% had mutations in the TERT promoter region. TERT promoter methylation was observed in all stages and grades of bladder cancer. While, TERT promoter mutations were detected in advanced stages and grades. In our cohort, high levels of TERT expression and long telomeres have been found in noninvasive cases of bladder cancer, with a significant association between TERT expression and Telomere length. Interestingly, patients with low TERT expression and cases with long telomeres had significantly longer Disease-free survival and overall survival. The methylation and mutations occurring in the TERT promoter are implicated in bladder carcinogenesis, offering added prognostic and supplying novel insight into telomere biology in cancer.
Sections du résumé
BACKGROUND
BACKGROUND
Telomerase activity plays a crucial role in cancer development and progression. Thus, telomerase activation through the interplay of mutations and epigenetic alterations in the telomerase reverse transcriptase (TERT) promoter may provide further insight into bladder cancer induction and progression.
METHODS
METHODS
In this study 100 bladder tumour tissues were selected, and four molecular signatures were analysed: THOR methylation status, TERT promotor mutation, telomere length, and TERT expression.
RESULTS
RESULTS
In our study, 88% of bladder cancer patients had an hypermethylation of the THOR region and 60% had mutations in the TERT promoter region. TERT promoter methylation was observed in all stages and grades of bladder cancer. While, TERT promoter mutations were detected in advanced stages and grades. In our cohort, high levels of TERT expression and long telomeres have been found in noninvasive cases of bladder cancer, with a significant association between TERT expression and Telomere length. Interestingly, patients with low TERT expression and cases with long telomeres had significantly longer Disease-free survival and overall survival.
CONCLUSION
CONCLUSIONS
The methylation and mutations occurring in the TERT promoter are implicated in bladder carcinogenesis, offering added prognostic and supplying novel insight into telomere biology in cancer.
Identifiants
pubmed: 39147693
pii: S1078-1439(24)00536-2
doi: 10.1016/j.urolonc.2024.06.024
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2024 Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.