Melanoma in children and adolescents: analysis of susceptibility genes in 123 Italian patients.

Background A polygenic inheritance involving high, medium and low penetrance genes has been suggested for melanoma susceptibility in adults, but genetic information is scarce for pediatric patients. Objective We aim to analyze the major high and intermediate melanoma risk genes, CDKN2A, CDK4, POT1, MITF and MC1R, in a large multicenter cohort of Italian children and adolescents, in order to explore the genetic context of pediatric melanoma and to reveal potential differences in heritability between children and adolescents METHODS: One-hundred-twenty-three patients ( Results Most patients carried MC1R variants (67%), while CDKN2A pathogenic variants were found in 9% of the cases, the MITF E318K in 2% of patients, and none carried CDK4 or the POT1 S270N pathogenic variant. Sporadic melanoma patients significantly differed from familial and multiple cases for the young age at diagnosis, unfrequent red hair color, low number of nevi, low frequency of CDKN2A pathogenic variants and of the MC1R R160W variant. Melanoma in children (≤ 12 years) had more frequently spitzoid histotype, were located on the head/neck and upper limbs and had higher Breslow thickness. The MC1R V92M variant was more common in children than in adolescents. CDKN2A common polymorphisms and MC1R variants were associated with a high number of nevi. Conclusion Our results confirm the scarce involvement of the major high-risk susceptibility genes in pediatric melanoma and suggest the implication of MC1R gene variants especially in the children population.