Analysis of the CDKN2A and CDK4 genes and HLA-DR and HLA-DQ alleles in two Spanish familial melanoma kindreds

Acta Derm Venereol. 2000 Nov-Dec;80(6):440-2. doi: 10.1080/000155500300012936.


Some confusion exists in the literature about which criteria should be used to define familial melanoma. This could explain the different reported frequencies of mutations in predisposing genes, mostly CDKN2A, in these patients. This study evaluated the human leucocyte antigen (HLA) class II genotype and the presence of mutations in CDKN2A and CDK4 genes in 2 families with very different clinical features. The family with a germinal mutation in exon 2 of CDKN2A (Gly101Try) presented the following clinical features: 3 first-degree affected members, 1 of whom had 2 melanomas, and all the melanomas appearing before 35 years of age. In contrast, the second family did not present any mutation in the studied genes and included 2 first-degree affected members diagnosed at over 45 years of age. Neither family showed an association with HLA genotype. Other genes are also involved in familial melanoma but, when the CDKN2A gene is affected, some clinical features seem to be uniform.

MeSH terms

  • Adult
  • Alleles
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinases / genetics*
  • Female
  • Genes, p16 / genetics*
  • Genetic Predisposition to Disease*
  • HLA-DQ Antigens / analysis
  • HLA-DQ Antigens / genetics*
  • HLA-DR Antigens / analysis
  • HLA-DR Antigens / genetics*
  • Humans
  • Male
  • Melanoma / genetics*
  • Middle Aged
  • Mutation
  • Pedigree
  • Proto-Oncogene Proteins*
  • Sensitivity and Specificity
  • Skin Neoplasms / genetics*
  • Spain


  • HLA-DQ Antigens
  • HLA-DR Antigens
  • Proto-Oncogene Proteins
  • CDK4 protein, human
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinases