PIF2024 - Fusiones telómericas alternativas en cáncer (PID2023-153010OB-I00)

Cancer cells achieve immortality by maintaining their telomeres, the protective caps on chromosomes, above a critical length. This is achieved either through the upregulation of telomerase or via an alternative lengthening mechanism, known as ALT. The choice of the telomere maintenance mechanism (TMM) employed by a tumor determines different treatment options. Therefore, identifying the TMM utilized by cancer cells is of critical importance. Recently, our group uncovered a novel aspect of cancer cells that use the ALT pathway for telomere maintenance (Muyas et al., Nat. Comm. 2024). We have identified a unique type of telomere fusion, which we refer to as ALT-TF, predominantly found in ALT-positive cancers. Interestingly, we also detected ALT-TFs in the blood samples of patients with these cancers. This finding positions ALT-TF as a potential biomarker for liquid biopsy, holding promise for cancer diagnosis, prognosis, and monitoring of treatment efficacy. Our new project aims to quantify ALT-TF levels in over 6,000 metastatic cancers across various types, expanding our understanding of this phenomenon. The selected candidate will identify key genes driving ALT-TF formation as well as treatments that trigger their presence in the bloodstream. Additionally, she/he will study the mechanisms behind ALT-TF generation and develop improved methods to detect them. Through these efforts, our objective is to pioneer novel diagnostic, prognostic, and treatment-informing approaches