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Développement d'un modèle de xénogreffe primaire de chordome en milieu orthotopique et étude biomoléculaire d'une série de 43 chordomes

Abstract : Chordoma is a rare bone tumor that develops from embryonic remnants derived from the fetal notochord. The future of chordoma management is linked to a better understanding of the molecular mechanisms that underlie oncogenesis and to the development of new therapeutic targets, based on investigations in relevant animal models.The role of cell cycle dysregulation in chordomagenesis has been the focus of several studies. The objective of this work was to establish a relevant animal model mimicking chordoma oncogenesis and then examine the cytogenetic alterations by a-CGH (Array comparative genomic hybridization), searching for genetic mutations in 84 cell cycle genes using NGS (Next sequencing generation).We developed a primary chordoma xenograft model in an orthotopic setting and showed that the engraftment rate was higher at orthotopic than at subcutaneous sites. The model demonstrated genomic and genetic stability after repeated passage. In addition, our molecular study of a series of 43 chordomas revealed distinct molecular profiles according to the two major locations of the tumor (sacrum, skull base). Several mutations of the ZBTB17 gene associated with the sacral location may be involved in the oncogenesis of sacral chordoma. These new molecular data open up new perspectives on the oncogenetic mechanisms of chordoma.
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Submitted on : Wednesday, February 2, 2022 - 5:16:08 PM
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Henri Salle. Développement d'un modèle de xénogreffe primaire de chordome en milieu orthotopique et étude biomoléculaire d'une série de 43 chordomes. Médecine humaine et pathologie. Université de Limoges, 2021. Français. ⟨NNT : 2021LIMO0061⟩. ⟨tel-03553363⟩

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