Oral communication, CS15 / C65

Official XXIst International Pigment Cell Conference website - 21-24 Sept 2011, Bordeaux - France | updated: September 04 2011

Canine melanoma: promising spontaneous models for genetics and therapies of human melanoma

SPEAKER C. Andre #whois submiter ?
AUTHOR(s) M. Gillard, C. De Brito, J. Abadie, B. Vergier, A.-S. Guillory, E. Cadieu, P. Devauchelle, F. Galibert, B. Hédan, C. André

Melanoma spontaneously affect dogs on the same localizations than human: cutaneous, oral and ocular, with striking breed predispositions and we thus propose that dog breeds with high risk of melanoma constitute unique models to unravel the genetics of melanoma and prove useful for clinical trials. Indeed, melanoma diagnosed in several dog breeds, present clinical, histological and treatment response similarities with human melanoma. In addition, the dog population is structured in more than 350 breeds, which are rather heterogeneous between them, but strongly homogenous within breeds, thus resembling human isolated groups. Canine breeds spontaneously develop melanoma in a breed and tissue specific manner, with high risks (example: 3 to 5% of poodles develop melanoma, 99% of them of oral localization). Moreover, dog and human share similar environmental exposures and the relationship between melanoma and phototype can be largely explored with the variety of coat colours ! Due to a strong homology in the physiopathology and the response to treatments between dogs and humans, the discovery of new canine genes is expected to be transferred to human in a very promising way. These characteristics make the canine model ideal to identify predisposing and tumor progression genes in melanoma and shows an interesting potential for clinical trials. Our work consists in: 1. characterisation of the homology between dog and human melanoma types, 2. case/control genetic analyses to identify predisposing genes in high risk breeds 3. CGH and RNA sequencing analyses to identify tumour progression alterations. 1. A total of 150 clinical questionnaires of all localisation have been collected and analysed in order to characterize epidemiology and clinical data of dog melanoma compared to human. An histological confrontation between dog and human cases have been performed on 150 dog melanoma cases defining a canine classification and homologies to human. Moreover cDNA sequencing of a set of genes in dogs frequently altered in human melanoma has been undertook (Braf, Nras, Ckit, CDKN2A, Pten, MC1R and CDK4). 2. We have selected the poodle to undergo a Whole Genome Association Study with 100 cases and 100 healthy controls to search for loci predisposing to oral melanoma. 3. In the same time, tissue samples of tumour of different location and healthy tissue samples (100 tumour/control pairs have been collected so far) will be used for RNA sequencing and CGH analyses of oral and cutaneous dog melanoma. All together, these genetic analyses are thought to identify identical or novel genes and/or pathways in the different melanoma types to be able to transfer to human for a better understanding of the physiopathology and genetics of these tumours, and anticipate clinical trials on dogs for the most human homologous melanoma types.



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Université de Bordeaux 2 & Conseil Régional Aquitaine