Alterations in DNA Damage Repair Genes Before and After Neoadjuvant Cisplatin-based Chemotherapy in Muscle-invasive Bladder Cancer

Autor: Ursula Lemberger, Büsra Ernhofer, Sigurd Krieger, Andreas Bruchbacher, André Oszwald, Ekaterina Laukhtina, Andrea Haitl, Melanie R. Hassler, Bernhard Englinger, Eva Compérat, Shahrokh F. Shariat
Jazyk: angličtina
Rok vydání: 2025
Předmět:
Zdroj: European Urology Open Science, Vol 71, Iss , Pp 38-48 (2025)
Druh dokumentu: article
ISSN: 2666-1683
DOI: 10.1016/j.euros.2024.10.022
Popis: Background and objective: The role of genetic variants in response to systemic therapy in muscle-invasive bladder cancer (MIBC) is still elusive. We assessed variations in genes involved in DNA damage repair (DDR) before and after cisplatin-based neoadjuvant chemotherapy (NAC) and correlation of alteration patterns with DNA damage and response to therapy. Methods: Matched tissue from 46 patients with MIBC was investigated via Ion Torrent–based next-generation sequencing using a self-designed panel of 30 DDR genes. Phosphorylation of γ-histone 2A.X (H2AX) was analyzed via immunohistochemistry to evaluate DNA damage. Genetic variants were analyzed along with clinical data and quantitative phospho-H2AX data using the Kaplan-Meier method, Cox regression analysis, and factor analysis of mixed data. Key findings and limitations: Twenty-five patients (54%) had a response (
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