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Anabelle Decottignies – Institut de Duve: The alternative mechanism of telomere maintenance: a new relevant therapeutic target to investigate in children and young adolescent osteosarcoma


2016 - In Belgium, osteosarcoma remains the most predominant histological subtype of bone tumour in children and adolescent. Unlike what is observed in many other sarcomas, genetic alterations are not restricted to specific chromosome translocations, making it difficult to identify effective molecular targets for treatment. Consequently, protocols have not changed much over the last 10 years and 3-year disease-free survival rates have remained at about 60-70% for localized osteosarcomas. Ability to maintain telomeres is one of the main cancer cell hallmarks and is linked to cellular immmortalization. While about 90% of cancer cells manage to reactivate telomerase, cellular immortalization can also result from the activation of an alternative and telomerase-independent mechanism of telomere maintenance dubbed ALT (Alternative Lengthening of Telomeres). ALT activation is frequent in paediatric tumours and account for telomere maintenance in nearly 60% of osteosarcomas. The long-term objective of this project is to evaluate whether targeting the alternative mechanism of telomere maintenance would provide new possibilities of treatment for osteosarcoma. This 2 years project aims primarily at setting up and characterizing a new collection of primary paediatric osteosarcoma cell lines for testing this hypothesis.

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