CDKN2A mutations in Scottish families with cutaneous melanoma: results from 32 newly identified families

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Abstract
Up to 5% of patients with melanoma have a family history of a first-degree relative also being affected. To study such families for germline mutations, to help clarify the gene-environment interaction in melanoma aetiology. Thirty-two families in Scotland with melanoma in two or more first-degree relatives are reported for the first time. Peripheral blood DNA was extracted, and denaturing high-performance liquid chromatography analysis performed on exons 1alpha and 2 of the CDKN2A gene and their splice junctions. The coding sequences and splice junctions of these exons were sequenced in all samples as confirmation of the chromatographic pattern observed. Seven of the 32 melanoma families (22%) have CDKN2A mutations. One mutation, H83N, which has not previously been described in melanoma families, was found in one family. In addition, two families have R112G mutations, one family has a G67R mutation, one has an exon 1alpha 24-bp duplication where bases 9-32 are duplicated between bases 32 and 33, and two families have M53I mutations, bringing the total of known Scottish families with the M53I mutation to six. This study brings the total of Scottish families investigated for germline mutations to 48, and strongly suggests that the M53I mutation originated in Scotland.