{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T10:16:59Z","timestamp":1785493019522,"version":"3.56.0"},"reference-count":27,"publisher":"Mattioli1885","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Introduction: Approximately 20%-45% of familial melanoma (FM) cases are associated with genetic predisposition. Objectives: This single-center retrospective study aimed to assess the frequency of pathogenic variants (PV) in the main melanoma-predisposing genes in patients with cutaneous melanoma and investigate the clinical predictors of genetic predisposition. Methods: Patients included were those diagnosed with cutaneous melanoma at the Dermatology Unit of the University Hospital, Verona, Italy, from 2000 to 2022, presenting at least one of the following: multiple melanomas (\u22653); personal\/family history of pancreatic cancer (PC) (up to second-degree relatives); \u22652 first-degree relatives with melanoma; \u22651 first-degree relatives with early onset (&lt;45 years) melanoma and tested for CDKN2A, CDK4, POT1, BAP1, MITF, ATM, and TERT. Results: During the study period, 35 out of 1,320 patients (2.7%) underwent genetic testing. Four patients (11.4%) harbored a PV in a melanoma-predisposing gene, 3 in CDKN2A (8.6%), and 1 in MITF (2.9%). Variants currently classified as being of unknown clinical significance (VUS) were detected in CDKN2A (n=1), MITF (n=1), and ATM (n=2). Family history of PC and \u22655 melanomas, personal history of \u226550 nevi, and \u22654 melanomas were significantly associated with PV in tested genes (P&lt;0.05). Conclusions: The prevalence of PV in predisposing genes in FM was lower than previously reported in Italian registries. Possible reasons include deleterious variants in untested intermediate-\/low-penetrance genes or yet-to-be-discovered high-penetrance genes and environmental risk factors. A family history of PC, a high number of nevi and melanomas predict a monogenic predisposition to melanoma.<\/jats:p>","DOI":"10.5826\/dpc.1403a120","type":"journal-article","created":{"date-parts":[[2024,7,31]],"date-time":"2024-07-31T14:33:34Z","timestamp":1722436414000},"page":"e2024120","source":"Crossref","is-referenced-by-count":4,"title":["Prevalence of CDKN2A, CDK4, POT1, BAP1, MITF, ATM, and TERT Pathogenic Variants in a Single-Center Retrospective Series of Patients With Melanoma and Personal or Family History Suggestive of Genetic Predisposition"],"prefix":"10.5826","volume":"14","author":[{"given":"Giada","family":"Ferrara","sequence":"first","affiliation":[{"name":"Section of Dermatology and Venereology, Department of Medicine, University of Verona, Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Paiella","sequence":"additional","affiliation":[{"name":"Pancreatic Surgery Unit, Pancreas Institute, University of Verona, Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulio","family":"Settanni","sequence":"additional","affiliation":[{"name":"Pathology Unit, IRCCS Sacro Cuore Don Calabria Hospital, Negrar di Valpolicella, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Frizziero","sequence":"additional","affiliation":[{"name":"Cancer Research UK Manchester Institute Cancer Biomarker Centre, Manchester, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Rosina","sequence":"additional","affiliation":[{"name":"Section of Dermatology and Venereology, Department of Medicine, University of Verona, Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Viassolo","sequence":"additional","affiliation":[{"name":"Medical Genetics, IRCCS Sacro Cuore Don Calabria Hospital, Negrar di Valpolicella, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"27750","published-online":{"date-parts":[[2024,7,31]]},"reference":[{"key":"10.5826\/dpc.1403a120_ref1","unstructured":"Truderung OA, Sagi JC, Semsei AF, Szalai C: Melanoma susceptibility: an update on genetic and epigenetic findings. 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