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PLoS One. 2015 Mar 24;10(3):e0122662. doi: 10.1371/journal.pone.0122662. eCollection 2015.

Molecular characterization of melanoma cases in Denmark suspected of genetic predisposition.

Author information

1
Department of Clinical Genetics, University Hospital of Copenhagen, Copenhagen, Denmark.
2
QIMR Berghofer Medical Research Institute, Brisbane, Australia.
3
Department of Clinical Genetics, University hospital of Odense, Odense, Denmark.
4
Department of Clinical Genetics, University hospital of Århus, Århus, Denmark.
5
Department of Clinical Genetics, Vejle hospital, Lillebaelt Hospital, Vejle, Denmark.
6
Department of Clinical Genetics, University Hospital of Copenhagen, Copenhagen, Denmark; Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, Denmark.
7
Department of Oncology, Lund University and Skåne University Hospital, Lund, Sweden.
8
Department of Ophthalmology, Glostrup Hospital, University of Copenhagen, Denmark; Eye Pathology Institute, Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
9
Department of Ophthalmology, Glostrup Hospital, University of Copenhagen, Denmark.
10
Center for Genomic Medicine, Rigshospitalet, Copenhagen University hospital, Copenhagen, Denmark.
11
Department of Plastic Surgery, Breast Surgery and Burns, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark.

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.

PMID:
25803691
PMCID:
PMC4372390
DOI:
10.1371/journal.pone.0122662
[Indexed for MEDLINE]
Free PMC Article

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