Retrospective study of germline variants in patients with hereditary melanoma study criteria in a real clinical practice setting

Abstract Background Five to twelve per cent of melanoma cases show aggregation of melanomas or other related tumours within the same family or individual. Genes such as CDKN2A or BAP1, among others, have been associated with this condition. Objectives To describe the epidemiology and clinical characteristics of patients in whom a germline genetic study was performed due to suspected hereditary melanoma. Methods This was a retrospective descriptive study that included patients from Cruces University Hospital who underwent a germline genetic analysis for hereditary melanoma from 2016 to 2023, having met any of the following criteria: (i) presence of two or more melanomas in the same individual; (ii) a melanoma and a pancreatic cancer in the same individual; (iii) presence of a melanoma in an individual and one or more first- or second-degree relatives with melanoma or pancreatic cancer; (iv) first- or second-degree relative of an individual with a known deleterious variant in genes associated with melanoma predisposition; or (v) incidental discovery of deleterious variants in genes associated with predisposition to melanoma, within hereditary cancer panels carried out for reasons other than melanoma. Results In total, 59 families were included, comprising 69 patients (64% women). Among these, 8% of families (13% of patients) presented pathogenic/likely pathogenic (P/LP) variants: 6% of families (6% of patients), excluding criteria (iv) and (v), showed P/LP variants in CDKN2A, and 2% of families (1% of patients) presented P/LP variants in BAP1, BRCA2 and TERF2IP. Conclusions The frequencies of P/LP variants in CDKN2A are similar to those previously described. This study could contribute to the knowledge of the characteristics of patients who meet genetic study criteria for hereditary melanoma in a setting of real-world clinical practice.