Genetic susceptibility in familial melanoma from northeastern Italy

Cutaneous malignant melanoma (CMM) is a potentially fatal form of skin cancer, whose incidence and mortality are increasing in the Western world.1,2 Approximately 3–12% of cutaneous malignant melanoma develops in families with multiple cases of melanoma.3–5 Worldwide studies of large families prone to melanoma have demonstrated linkage to a locus on chromosome 9p21 (MIM 600160) in the majority of kindreds, and probable linkage to 1p22 6 and 1p36 7,8 in others. About one third of 9p21 linked families carry mutations in the CDKN2A tumour suppressor gene,9,10 which encodes the p16 cell cycle inhibitor. Rare kindreds may also possess mutations of the coding sequences of CDK4 (MIM 12829),11,12 or p14ARF (translated from exons 1β and 2 of CDKN2A ).13–15 More studies are needed to understand the genetic basis of melanoma. In Italy, the melanoma prone families studied to date are mostly from the north16 and northwestern areas,15,17,18 the centre,19 and the Sardinia region.20 These families are generally characterised by small numbers of melanoma cases, and a relatively high frequency of CDKN2A mutations. We studied families prone to melanoma from northeastern Italy, to characterise genetic susceptibility to melanoma in this population. ### Study population The study group was comprised of 55 families: 44 (80%) from southern Emilia Romagna and northern Marche (close to the border between the two regions); 10 families, all with two cases per family, from other areas of Italy (four from the south, three from the centre, two from the north, and one from Sardinia), and one family from Russia. All the families were recruited at the Dermatology Unit of the Bufalini Hospital in Cesena, Italy. Bufalini Hospital’s and the National Cancer Institute’s Ethical Committees approved the study, and written informed consent was obtained …