TERT Promoter Mutations as a Universal Urine Biomarker for Bladder Cancer Detection

• Applicant: Dr. Viktoria Menzel
• Subject Area: Reproductive Medicine, Urology
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 580313260

Bladder cancer represents a major global health challenge, with more than 500,000 new cases annually. In sub-Saharan Africa, particularly in Malawi, squamous cell carcinoma of the bladder associated with chronic schistosomiasis is highly prevalent, progresses aggressively, and remains insufficiently studied. Current diagnostics rely on cystoscopy—an invasive and costly procedure unsuitable for population-based screening and early detection. Despite decades of research, no validated non-invasive biomarker exists, leaving a critical diagnostic gap. This gap is especially relevant in sub-Saharan Africa, where infection-related bladder cancer remains common, as well as in Europe, where the overall disease burden is high. Both settings could benefit from the development of a universal, urine-based biomarker enabling earlier and more accessible diagnosis. Research at the International Agency for Research on Cancer of the World Health Organization (IARC/WHO) in Lyon has demonstrated that mutations in the promoter region of the TERT gene—the most frequent genetic alteration in bladder cancer—can be reliably detected in urine. Highly sensitive detection assays developed and validated at IARC have shown diagnostic performance superior to urine cytology and provided evidence that TERT promoter mutations can be present in urine years before clinical diagnosis. Although these findings highlight the potential of TERT promoter mutations as early, non-invasive biomarkers, they have not yet been systematically evaluated in a high-incidence cohort. This project will address this gap by analyzing tumor and urine samples collected from patients and controls in Malawi at the IARC/WHO in Lyon. By combining local sample collection in a high-incidence region with state-of-the-art molecular analysis in a world-leading cancer research environment, it provides a unique opportunity to assess the diagnostic utility of urinary TERT promoter mutations under conditions of high clinical relevance. The project pursues three main objectives: (i) to characterize TERT promoter mutations in tumor tissue, (ii) to investigate their detectability in urine to evaluate their potential as a non-invasive biomarker for bladder cancer diagnosis, and (iii) to link molecular profiles with pathogen data to identify infection-related risk factors. The research will be conducted at the IARC/WHO in Lyon, applying advanced high-sensitivity assays for mutation analysis. The results will be transferred to the University Hospital Dresden to strengthen biomarker-based bladder cancer research and establish a sustainable international collaboration. By focusing specifically on TERT promoter mutations, the project aims to explore their potential as a basis for improved, non-invasive approaches to bladder cancer detection.

• DFG Programme: WBP Fellowship
• International Connection: France
• Host: Dr. Florence Le Calvez-Kelm