New susceptibility loci for cutaneous melanoma risk and progression revealed using a porcine model.

Despite major advances, it is estimated that a large part of melanoma predisposing genes remains to be discovered. Animal models of spontaneous diseases are valuable tools and experimental crosses can be used to identify and fine-map new susceptibility loci associated with melanoma. We performed a Genome-Wide Association Study (GWAS) of melanoma occurrence and progression (clinical ulceration and presence of metastasis) in a porcine model of spontaneous melanoma, the MeLiM pig. Five loci on chromosomes 2, 5, 7, 8 and 16 showed genome-wide significant associations ( < 5 × 10) with either one of these phenotypes. Suggestive associations ( < 5 × 10) were also found at 16 additional loci. Moreover, comparison of the porcine results to those reported by human melanoma GWAS indicated shared association signals notably at and loci but also nearby , FTO, and TMEM loci. Extensive search of the literature revealed a potential key role of genes at the identified porcine loci in tumor invasion (, PLEKHA5, , and ) and immune response modulation (, and ) of the progression phenotypes. These biological processes are consistent with the clinico-pathological features of MeLiM tumors and can open new routes for future melanoma research in humans.