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. 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

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Free PMC article

Molecular Characterization of Melanoma Cases in Denmark Suspected of Genetic Predisposition

Karin A W Wadt et al. PLoS One. .
Free PMC article

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.

Conflict of interest statement

Competing Interests: LGA was supported by a PhD scholarship from the Australia and New Zealand Banking Group Limited Trustees; this does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1
Fig 1. Flow-chart of melanoma cases included in the study.
Fig 2
Fig 2. Age-specific penetrance curves for CM in Danish CDKN2A mutation carriers.

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Grant support

The Nordic Cancer Union provided funds to KW and GJ (http://www.ncu.nu/). Rigshospitalet funded KW with a PhD scholarship. Fight for sight funded KW (http://www.vos.dk/). Aase and Ejnar Danielsens Fund funded KW (http://www.danielsensfond.dk). Fonden til lægevidenskabens fremme funded KW (http://www.apmollerfonde.dk/). NH was supported by a fellowship from the National Health and Medical Research Council of Australia. LA was supported by a PhD scholarship from the Australia and New Zealand Banking Group Limited Trustees. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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