Melanoma-prone families with CDK4 germline mutation: Phenotypic profile and associations with MC1R variants

Families with mutations in the genes CDKN2A or CDK4 have a very high risk of developing cutaneous malignant melanoma. CDKN2A melanoma families are well characterized, whereas a common description has been lacking for the much rarer CDK4 families. We have studied 17 CDK4 families from eight countries, the largest collection of such pedigrees to date. In these families, there were altogether 103 subjects with a diagnosis of melanoma. They were characterized by early onset of disease, increased occurrence of clinically atypical nevi, development of multiple primary melanomas and an influence of MC1R gene variants on the phenotype. We conclude that CDK4 families cannot be distinguished phenotypically from those with CDKN2A mutation. In a clinical setting, the CDK4 gene should therefore always be examined in melanoma families with negative CDKN2A status. (By Dr. Hanne Eknes Puntervoll, http://jmg.bmj.com/content/early/2013/02/04/jmedgenet-2012-101455 )