The genetics of cutaneous melanoma

Clin Lab Med. 2000 Dec;20(4):667-90.


Although germline mutations in CDKN2A are present in approximately 25% of large multicase melanoma families, germline mutations are much rarer in the smaller melanoma families that make up most individuals reporting a family history of this disease. In addition, only three families worldwide have been reported with germline mutations in a gene other than CDKN2A (i.e., CDK4). Accordingly, current genomewide scans underway at the National Human Genome Research Institute hope to reveal linkage to one or more chromosomal regions, and ultimately lead to the identification of novel genes involved in melanoma predisposition. Both CDKN2A and PTEN have been identified as genes involved in sporadic melanoma development; however, mutations are more common in cell lines than uncultured tumors. A combination of cytogenetic, molecular, and functional studies suggests that additional genes involved in melanoma development are located to chromosomal regions 1p, 6q, 7p, 11q, and possibly also 9p and 10q. With the near completion of the human genome sequencing effort, combined with the advent of high throughput mutation analyses and new techniques including cDNA and tissue microarrays, the identification and characterization of additional genes involved in melanoma pathogenesis seem likely in the near future.

Publication types

  • Review

MeSH terms

  • Cluster Analysis
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • Cyclin-Dependent Kinases / genetics
  • DNA, Neoplasm / analysis
  • Disease Progression
  • Genes, p16 / genetics
  • Germ-Line Mutation
  • Humans
  • Melanoma / genetics*
  • Mutation
  • Oligonucleotide Array Sequence Analysis / methods
  • PTEN Phosphohydrolase
  • Phosphoric Monoester Hydrolases / genetics
  • Proto-Oncogene Proteins*
  • Skin Neoplasms / genetics*
  • Tumor Suppressor Proteins*


  • Cyclin-Dependent Kinase Inhibitor p16
  • DNA, Neoplasm
  • Proto-Oncogene Proteins
  • Tumor Suppressor Proteins
  • CDK4 protein, human
  • Cyclin-Dependent Kinase 4
  • Cyclin-Dependent Kinases
  • Phosphoric Monoester Hydrolases
  • PTEN Phosphohydrolase
  • PTEN protein, human