Tumeurs des maxillaires avec anomalies du développement : à partir des modèles de tumeurs kératokystiques odontogènes et du chérubinisme

Abstract : To determine pathophysiological bases of jawbone tumors, we studied two genetic models of jawbone tumors: keratocystic odontogenic tumors (KOT) associated to PTCH1 mutation and cherubism associated to SH3BP2 mutation. From oncogenetic theory, we postulate that genetic background controls the development of benign children jawbone tumors. From our work, we demonstrated that PTCH1 mutation (germline mutation in Gorlin syndrome) was an unfavorable prognosis factor for KOT, leading to distant and independent daughter tumors. Moreover, we showed, that chorionic inflammation was associated with a high recurrence rate. In cherubism, SH3BP2 mutation produced cherubism phenotype, but the type of mutation did not affect the aggressiveness of the disease. Cherubism aggressiveness was determined by the phenotype of giant multinucleated cells (whether osteoclasts or macrophages). Furthermore, we showed that murine model could not be transposed to human pathology; indeed it appeared that TNF- α did not play a critical role in human cherubism. On the other side, we showed that NFATc1 played a crucial role in cherubism pathophysiology; this observation allowed us to propose, the tacrolimus, as an effective treatment for this disease. Our results suggest that genetic background induced tumor development, and that microenvironment changes (due to flora of the oral cavity and to teeth eruptions) are responsible to the maintenance and the progression of the disease.
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Natacha Kadlub. Tumeurs des maxillaires avec anomalies du développement : à partir des modèles de tumeurs kératokystiques odontogènes et du chérubinisme. Biologie cellulaire. Université Sorbonne Paris Cité, 2015. Français. ⟨NNT : 2015USPCB080⟩. ⟨tel-01409974⟩

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