title: Molecular characterization of melanoma cases in Denmark suspected of genetic predisposition.
abstract: Both environmental and host factors influence risk of cutaneous melanoma (CM), and worldwide, the incidence varies depending on constitutional determinants of skin type and pigmentation, latitude, and patterns of sun exposure. We performed genetic analysis of CDKN2A, CDK4, BAP1, MC1R, and MITFp.E318K in Danish high-risk melanoma cases and found CDKN2A germline mutations in 11.3% of CM families with three or more affected individuals, including four previously undescribed mutations. Rare mutations were also seen in CDK4 and BAP1, while MC1R variants were common, occurring at more than twice the frequency compared to Danish controls. The MITF p.E318K variant similarly occurred at an approximately three-fold higher frequency in melanoma cases than controls. To conclude, we propose that mutation screening of CDKN2A and CDK4 in Denmark should predominantly be performed in families with at least 3 cases of CM. In addition, we recommend that testing of BAP1 should not be conducted routinely in CM families but should be reserved for families with CM and uveal melanoma, or mesothelioma.
authors: Department of Clinical Genetics, University Hospital of Copenhagen, Copenhagen, Denmark.
authors: Karin A W
authors: KA
authors: Wadt
authors: QIMR Berghofer Medical Research Institute, Brisbane, Australia.
authors: Lauren G
authors: LG
authors: Aoude
authors: Department of Clinical Genetics, University hospital of Odense, Odense, Denmark.
authors: Lotte
authors: L
authors: Krogh
authors: Department of Clinical Genetics, University hospital of Århus, Århus, Denmark.
authors: Lone
authors: L
authors: Sunde
authors: Department of Clinical Genetics, Vejle hospital, Lillebaelt Hospital, Vejle, Denmark.
authors: Anders
authors: A
authors: Bojesen
authors: Department of Clinical Genetics, University Hospital of Copenhagen, Copenhagen, Denmark; Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark.
authors: Karen
authors: K
authors: Grønskov
authors: Department of Clinical Genetics, University Hospital of Copenhagen, Copenhagen, Denmark.
authors: Nine
authors: N
authors: Wartacz
authors: Department of Clinical Genetics, University Hospital of Copenhagen, Copenhagen, Denmark.
authors: Jakob
authors: J
authors: Ek
authors: Department of Clinical Genetics, University Hospital of Copenhagen, Copenhagen, Denmark.
authors: Morten
authors: M
authors: Tolstrup-Andersen
authors: Department of Clinical Genetics, University Hospital of Copenhagen, Copenhagen, Denmark.
authors: Mette
authors: M
authors: Klarskov-Andersen
authors: Department of Oncology, Lund University and Skåne University Hospital, Lund, Sweden.
authors: Åke
authors: Å
authors: Borg
authors: Department of Ophthalmology, Glostrup Hospital, University of Copenhagen, Denmark; Eye Pathology Institute, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
authors: Steffen
authors: S
authors: Heegaard
authors: Department of Ophthalmology, Glostrup Hospital, University of Copenhagen, Denmark.
authors: Jens F
authors: JF
authors: Kiilgaard
authors: Center for Genomic Medicine, Rigshospitalet, Copenhagen University hospital, Copenhagen, Denmark.
authors: Thomas V O
authors: TV
authors: Hansen
authors: QIMR Berghofer Medical Research Institute, Brisbane, Australia.
authors: Kerenaftali
authors: K
authors: Klein
authors: Department of Oncology, Lund University and Skåne University Hospital, Lund, Sweden.
authors: Göran
authors: G
authors: Jönsson
authors: Department of Plastic Surgery, Breast Surgery and Burns, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.
authors: Krzysztof T
authors: KT
authors: Drzewiecki
authors: Department of Clinical Genetics, University Hospital of Copenhagen, Copenhagen, Denmark.
authors: Morten
authors: M
authors: Dunø
authors: QIMR Berghofer Medical Research Institute, Brisbane, Australia.
authors: Nicholas K
authors: NK
authors: Hayward
authors: Department of Clinical Genetics, University Hospital of Copenhagen, Copenhagen, Denmark.
authors: Anne-Marie
authors: AM
authors: Gerdes
mesh_terms: D051358:Cyclin-Dependent Kinase 4; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D003718:Denmark / Q000453:epidemiology; D052138:Genes, Neoplasm / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing / Q000592:standards*; D018095:Germ-Line Mutation / Q000235:genetics; D006801:Humans; D008545:Melanoma / Q000453:epidemiology* / Q000235:genetics*; D051739:Microphthalmia-Associated Transcription Factor; D044102:Receptor, Melanocortin, Type 1; D012878:Skin Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D025521:Tumor Suppressor Proteins; D043222:Ubiquitin Thiolesterase
chemical_list: C400134:BAP1 protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; C497234:MITF protein, human; D051739:Microphthalmia-Associated Transcription Factor; D044102:Receptor, Melanocortin, Type 1; D025521:Tumor Suppressor Proteins; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D043222:Ubiquitin Thiolesterase