title: Melanoma risk alleles are associated with downregulation of the MTAP gene and hypermethylation of a CpG island upstream of the gene in dermal fibroblasts.
abstract: Several association studies and GWAS on melanoma skin cancer risk have reported statistically significant signals on 9p21.3 region, where MTAP gene maps. None of the associated SNPs identified in these studies lie in the coding region of the gene and the causative relation of risk alleles with melanoma predisposition has not been elucidated. MTAP has a tumor suppressor activity and epigenetic silencing has been described in melanoma cell lines. In the present study, we show that melanoma risk alleles correlate with a MTAP allele-specific hyper-methylation and down-regulation of gene expression.
authors.affiliation: Department of Neurosciences, Biomedicine and Movement Sciences, Section of Biology and Genetics, University of Verona, Verona, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Sangalli
authors.affiliation: Department of Neurosciences, Biomedicine and Movement Sciences, Section of Biology and Genetics, University of Verona, Verona, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Malerba
authors.affiliation: Section of Dermatology and Venereal Diseases, Department of Medicine, University of Verona, Verona, Italy.
authors.forename: Gianpaolo
authors.initials: G
authors.lastname: Tessari
authors.affiliation: Unit of Immunotherapy, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Rodolfo
authors.affiliation: Department of Neurosciences, Biomedicine and Movement Sciences, Section of Biology and Genetics, University of Verona, Verona, Italy.
authors.forename: Macarena
authors.initials: M
authors.lastname: Gomez-Lira
mesh_terms: D022981:Allelic Imbalance; D016022:Case-Control Studies; D018899:CpG Islands; D019175:DNA Methylation; D005347:Fibroblasts / Q000378:metabolism*; D006239:Haplotypes; D006801:Humans; D008545:Melanoma / Q000235:genetics*; D011683:Purine-Nucleoside Phosphorylase / Q000235:genetics* / Q000378:metabolism
chemical_list: D011683:Purine-Nucleoside Phosphorylase; C021784:5'-methylthioadenosine phosphorylase
keywords:  allele-specific expression; allele-specific methylation; genome-wide association study; melanoma skin cancer