Clinical features predicting identification of CDKN2A mutations in Italian patients with familial cutaneous melanoma

CDKN2A is the most common, most penetrant gene whom germline mutations predisposing to cutaneous familial melanoma (FAM). Multiple primary melanoma (MPM), early age at onset, >2 affected members and pancreatic cancer are consistent features predicting positive test. However, the impact that cumulative clinical features have on the likelihood of molecular testing is unknown. In this work, genotype-phenotype correlations focused on selected clinical features were performed in 100 Italian FAM unrelated patients. Molecular studies of CDKN2A mutations were performed by direct sequencing. Statistical study included multiple correspondence analysis, uni- and multivariate analyses, and individual patient's probability calculation. MPM, >2 affected family members, Breslow thickness >0.4. mm, and age at onset ≤41 years were the unique independent features predicting positive CDKN2A screening. The rate of positive testing ranged from 93.2% in the presence of all of them, to 0.4% in their absence. The contribution of each of them was quantified accordingly, with MPM being the most significant. These findings confirm previous data and add novel insights for the role of accurate patients' selection in CDKN2A screening.