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Le génome remanié comme oncogène des sarcomes pléomorphes ?

Abstract : Sarcomas with a complex genetics are rare tumours from mesenchymal tissue. They are characterized by massive chromosomal without any recurrent and specific alteration. The objective of my thesis was to identify the consequences of this chromosomal complexity and mechanisms explaining how this could be generated. First, transcriptome of 112 sarcomas with a complex genetics have been analysed. Chimeric transcripts detection and validation permitted the identification of frequent rearrangements in TRIO gene. These transcripts lead to the formation of a truncated protein and they would originate from a global rearrangement of the tumour genomes. Second, we have sought the origin of these alterations, with a particular interest for the cell fusion as an initiator mechanism. This physiological process is observed in mesenchymal cells like macrophages and myoblasts and it can be hijacked to drive tumour inception and evolution. I consequently studied both genomic and phenotypic consequences of hybrids from fibroblasts at different immortalization steps or in the different cell cycle phases. This work permitted to demonstrate that cell fusion mechanism leads to the initiation of genetic alterations that mimics the ones in sarcomas with complex genetics and would contribute to their tumour initiation and progression.
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Lucile Delespaul. Le génome remanié comme oncogène des sarcomes pléomorphes ?. Médecine humaine et pathologie. Université de Bordeaux, 2018. Français. ⟨NNT : 2018BORD0374⟩. ⟨tel-02433190⟩



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