| Abstract |
My PhD is in the frame of the comparative oncology field about the genetic
study of mucosal melanoma (MM) in dogs, that spontaneously develop oral
melanoma, frequent in some breed and severe. Thus, it constitutes a good
natural model for 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. 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 signedcomplex chromosomal rearrangements, as it is seen in
human MM. In the same time, the 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 structural variants
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 opens
therapeutic perspectives to benefit human and veterinary oncology for non
UV-induced melanomas.
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