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Cellosaurus publication CLPUB00708
| Publication number | CLPUB00708 |
|---|---|
| Authors | Prouteau A. |
| Title | Canine mucosal melanoma as a genetic and therapeutic model for human mucosal melanoma. |
| Citation | Thesis PhD (2020); Universite de Rennes; Rennes; France |
| Web pages | https://tel.archives-ouvertes.fr/tel-03199443 |
| 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. |
| Cell lines | CVCL_0D14; Bear CVCL_IZ11; CML-10 CVCL_C0MM; Dog-OralMel-18249 CVCL_C0MN; Dog-OralMel-18333 CVCL_C0MP; Dog-OralMel-18395 CVCL_C0MQ; Dog-OralMel-18657 CVCL_C0MR; Dog-OralMel-18848 |