Prevalence of Germline BAP1, CDKN2A, and CDK4 Mutations in an Australian Population-Based Sample of Cutaneous Melanoma Cases

Twin Res Hum Genet. 2015 Apr;18(2):126-33. doi: 10.1017/thg.2015.12. Epub 2015 Mar 19.


Mutations in Cyclin-Dependent Kinase Inhibitor 2A (CDKN2A) and Cyclin-Dependent Kinase 4 (CDK4) contribute to susceptibility in approximately 40% of high-density cutaneous melanoma (CMM) families and about 2% of unselected CMM cases. BRCA-1 associated protein-1 (BAP1) has been more recently shown to predispose to CMM and uveal melanoma (UMM) in some families; however, its contribution to CMM development in the general population is unreported. We sought to determine the contribution of these genes to CMM susceptibility in a population-based sample of cases from Australia. We genotyped 1,109 probands from Queensland families and found that approximately 1.31% harbored mutations in CDKN2A, including some with novel missense mutations (p.R22W, p.G35R and p.I49F). BAP1 missense variants occurred in 0.63% of cases but no CDK4 variants were observed in the sample. This is the first estimate of the contribution of BAP1 and CDK4 to a population-based sample of CMM and supports the previously reported estimate of CDKN2A germline mutation prevalence.

Keywords: germline mutation.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Australia / epidemiology
  • Cyclin-Dependent Kinase 4 / genetics*
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics*
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Melanoma / epidemiology
  • Melanoma / genetics*
  • Mutation*
  • Prevalence
  • Skin Neoplasms / epidemiology
  • Skin Neoplasms / genetics*
  • Tumor Suppressor Proteins / genetics*
  • Ubiquitin Thiolesterase / genetics*


  • BAP1 protein, human
  • Cyclin-Dependent Kinase Inhibitor p16
  • Tumor Suppressor Proteins
  • CDK4 protein, human
  • Cyclin-Dependent Kinase 4
  • Ubiquitin Thiolesterase