title: Prevalence of Germline BAP1, CDKN2A, and CDK4 Mutations in an Australian Population-Based Sample of Cutaneous Melanoma Cases.
abstract: 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.
authors: QIMR Berghofer Medical Research Institute,Brisbane,Queensland,Australia.
authors: Lauren G
authors: LG
authors: Aoude
authors: QIMR Berghofer Medical Research Institute,Brisbane,Queensland,Australia.
authors: Michael
authors: M
authors: Gartside
authors: QIMR Berghofer Medical Research Institute,Brisbane,Queensland,Australia.
authors: Peter
authors: P
authors: Johansson
authors: QIMR Berghofer Medical Research Institute,Brisbane,Queensland,Australia.
authors: Jane M
authors: JM
authors: Palmer
authors: QIMR Berghofer Medical Research Institute,Brisbane,Queensland,Australia.
authors: Judith
authors: J
authors: Symmons
authors: QIMR Berghofer Medical Research Institute,Brisbane,Queensland,Australia.
authors: Nicholas G
authors: NG
authors: Martin
authors: QIMR Berghofer Medical Research Institute,Brisbane,Queensland,Australia.
authors: Grant W
authors: GW
authors: Montgomery
authors: QIMR Berghofer Medical Research Institute,Brisbane,Queensland,Australia.
authors: Nicholas K
authors: NK
authors: Hayward
mesh_terms: D001315:Australia / Q000453:epidemiology; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008545:Melanoma / Q000453:epidemiology / Q000235:genetics*; D009154:Mutation; D015995:Prevalence; D012878:Skin Neoplasms / Q000453:epidemiology / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D043222:Ubiquitin Thiolesterase / Q000235:genetics*
chemical_list: C400134:BAP1 protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D025521:Tumor Suppressor Proteins; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D043222:Ubiquitin Thiolesterase
keywords: germline mutation