Study of canine mucous melanoma as a genetic and therapeutic model of human mucous melanoma.
Team dog genetics
Under the direction of Drs Catherine André and Benoît Hédan
My thesis is in the comparative oncology field and concerned the genetic study of mucosal melanoma (MM) in dogs, that spontaneously develop oral melanoma, frequent in some breed and highly severe.
Thus, it constitutes a good natural model to study human MM that is rare and very aggressive. The exome sequencing analysis of 70 canine MM cases by the team allowed to identify recurrent somatic alterations. I first focused on amplifications on canine chromosome (CFA) 10 and 30. On a cohort of 73 cases, I showed that the amplification of CFA 30 had a prognostic value (median survival time of 159 days vs. 317 days).
We showed that amplified genes were also overexpressed and had a role on tumour cell proliferation. The whole genome sequencing of canine cell lines showed that those amplifications signed complex chromosomal rearrangements, as it is seen in human MM.
In the same time, transcriptomic analysis of 32 canine MM samples showed the existence of two molecular subgroups: the first characterized by the overexpression of genes related to immune microenvironment, and the second by overexpression of oncogenes like TERT and MITF. Moreover, those groups differ in their SV content, more important in the second one. Those results suggest the use of different therapies, immunotherapy and targeted therapy respectively.
This work allowed to better characterize genetics of canine MM and open therapeutic perspectives with veterinary clinical trials, to benefit human and veterinary oncology for non UV-induced melanomas.
The jury will be composed of :
- Sophie Tartare-Deckert, Directeur de recherche Inserm,C3M, Université Nice Côte d'Azur
- Frédérique Ponce, Professeur, VetAgro-Sup, Université de Lyon
- Jean-Christophe Marine, Professeur, Université de Leuven, Belgique
- Anne Patsouris, PH, Institut de cancérologie de l'ouest site Paul Papin, Université d'Angers
- Eve Maubec, Professeur, Hôpital Avicenne, Université Paris 13
- Marie-Dominique Galibert, Professeur, UMR6290, Université Rennes 1, Rennes
- Benoît Hédan, UMR6290, Université Rennes 1, Rennes
- Catherine André, UMR6290, Université Rennes 1, Rennes