Identification of an ALT therapeutic target and re-evaluation of ALT markers in tumors and cell lines with long telomeres

Telomeres protect the ends of our chromosomes. The replicative immortality of cancer cells depends on the activation of a telomere maintenance mechanism: the telomerase or an alternative lengthening of telomeres (ALT) mechanism. ALT is activated in about 10% of tumors but this prevalence increases greatly in pediatric tumors. The latter are in need of targeted therapies but, to date, there is still no therapy targeting ALT. In this thesis, we identified TSPYL5 (testis-specific Y-encoded-like protein 5) as a critical protein for ALT+ cell viability, opening new perspectives for anti-ALT targeted therapies. We also established a mouse xenograft model with human ALT+ cancer cells to test the efficiency of future anti-ALT compounds. The lack of good tools for the diagnosis of ALT also led us to the development of a new robust test on tumor sections. Finally, we provided additional evidence that replicative stress induces some characteristics of ALT telomeres.
(BIFA - Sciences biomédicales et pharmaceutiques) -- UCL, 2022