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 due to rarity of the disease. Herein we report the results of the genetic analysis of major melanoma susceptibility genes in a cohort of Italian children and adolescent (<21 years) patients. Methods. A total of 123 patients from 9 centers were analysed for the following melanoma predisposing genes: CDKN2A, CDK4, POT1, MITF, and MC1R. The rate of gene mutations was compared between sporadic, familial and multiple melanoma patients and between children and adolescents, and their association with clinico-pathological characteristics was evaluated. Results. Overall, most patients carried MC1R variants (67%), while CDKN2A pathogenic mutations was found in 9% of the cases, the MITF E318K substitution in 2% of patients, and none carried CDK4 mutations or the POT1 S270N 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 mutations and of the MC1R R160W variant. Melanoma in children (<= 12 years) differed from that in adolescents for the more frequent spitzoid histotype, location on the head/neck and upper limbs and the higher Breslow thickness. The MC1R V92M variant was more common in children than in adolescents. Finally, CDKN2A common polymorphisms and MC1R variants were associated with red hair color and a high number of nevi; MC1R variants were also related to fair skin and lower Breslow thickness. Conclusions. 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.