Germline Non-CDKN2A Variants in Melanoma and Associated Hereditary Cancer Syndromes
The etiology of melanoma is multifactorial and arises from the interplay of genetic, phenotypic, and environmental factors. The genetic predisposition to melanoma is influenced by a complex interaction among genes exhibiting varying levels of penetrance (high, moderate, and low), each contributing d...
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2025-06-01
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| author | Chiara Anna Fiasconaro Alice Carbone Silvia Giordano Francesco Cavallo Paolo Fava Barbara Pasini Yuliya Yakymiv Sara Marchisio Pietro Quaglino Simone Ribero Gabriele Roccuzzo |
| author_facet | Chiara Anna Fiasconaro Alice Carbone Silvia Giordano Francesco Cavallo Paolo Fava Barbara Pasini Yuliya Yakymiv Sara Marchisio Pietro Quaglino Simone Ribero Gabriele Roccuzzo |
| author_sort | Chiara Anna Fiasconaro |
| collection | DOAJ |
| description | The etiology of melanoma is multifactorial and arises from the interplay of genetic, phenotypic, and environmental factors. The genetic predisposition to melanoma is influenced by a complex interaction among genes exhibiting varying levels of penetrance (high, moderate, and low), each contributing differently to the susceptibility of the disease. Furthermore, penetrance may vary based on the incidence of melanoma across diverse populations and geographical regions. Advances in genetic sequencing technologies have facilitated the identification of novel genes potentially associated with melanoma, as well as the characterization of relevant germline variants. While the most extensively researched variant is CDKN2A, recent studies have highlighted other variants unrelated to CDKN2A as significant areas of investigation. Among them, high-penetrance genes encompass CDK4, BAP1, POT1, TERT, ACD, and TERF2IP. In contrast, moderate-penetrance genes include MC1R, MITF, and SLC45A2, while low-penetrance genes consist of OCA2, TYRP1, and TYR. In addition to elevating the risk of melanoma, these genetic alterations may also predispose individuals to internal neoplasms. This review aims to provide a comprehensive overview of the definitions of sporadic, multiple primary, familial, and hereditary melanoma, with a particular emphasis on non-CDKN2A germline variants and their dermoscopic and phenotypic features. |
| format | Article |
| id | doaj-art-632adf196e0d4c8c81468960ea7c52f7 |
| institution | Kabale University |
| issn | 2079-9721 |
| language | English |
| publishDate | 2025-06-01 |
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| spelling | doaj-art-632adf196e0d4c8c81468960ea7c52f72025-08-20T03:27:14ZengMDPI AGDiseases2079-97212025-06-0113618010.3390/diseases13060180Germline Non-CDKN2A Variants in Melanoma and Associated Hereditary Cancer SyndromesChiara Anna Fiasconaro0Alice Carbone1Silvia Giordano2Francesco Cavallo3Paolo Fava4Barbara Pasini5Yuliya Yakymiv6Sara Marchisio7Pietro Quaglino8Simone Ribero9Gabriele Roccuzzo10Department of Medical Sciences, Section of Dermatology, University of Turin, 10126 Turin, ItalyDepartment of Medical Sciences, Section of Dermatology, University of Turin, 10126 Turin, ItalyDepartment of Medical Sciences, Section of Dermatology, University of Turin, 10126 Turin, ItalyDepartment of Medical Sciences, Section of Dermatology, University of Turin, 10126 Turin, ItalyDepartment of Medical Sciences, Section of Dermatology, University of Turin, 10126 Turin, ItalyMedical Genetics Unit, AOU ‘Città Della Salute e Della Scienza’, ‘Molinette’ Hospital, 10126 Turin, ItalyLaboratory of Immunogenetics, Department of Medical Sciences, University of Turin, 10126 Turin, ItalyLaboratory of Immunogenetics, Department of Medical Sciences, University of Turin, 10126 Turin, ItalyDepartment of Medical Sciences, Section of Dermatology, University of Turin, 10126 Turin, ItalyDepartment of Medical Sciences, Section of Dermatology, University of Turin, 10126 Turin, ItalyDepartment of Medical Sciences, Section of Dermatology, University of Turin, 10126 Turin, ItalyThe etiology of melanoma is multifactorial and arises from the interplay of genetic, phenotypic, and environmental factors. The genetic predisposition to melanoma is influenced by a complex interaction among genes exhibiting varying levels of penetrance (high, moderate, and low), each contributing differently to the susceptibility of the disease. Furthermore, penetrance may vary based on the incidence of melanoma across diverse populations and geographical regions. Advances in genetic sequencing technologies have facilitated the identification of novel genes potentially associated with melanoma, as well as the characterization of relevant germline variants. While the most extensively researched variant is CDKN2A, recent studies have highlighted other variants unrelated to CDKN2A as significant areas of investigation. Among them, high-penetrance genes encompass CDK4, BAP1, POT1, TERT, ACD, and TERF2IP. In contrast, moderate-penetrance genes include MC1R, MITF, and SLC45A2, while low-penetrance genes consist of OCA2, TYRP1, and TYR. In addition to elevating the risk of melanoma, these genetic alterations may also predispose individuals to internal neoplasms. This review aims to provide a comprehensive overview of the definitions of sporadic, multiple primary, familial, and hereditary melanoma, with a particular emphasis on non-CDKN2A germline variants and their dermoscopic and phenotypic features.https://www.mdpi.com/2079-9721/13/6/180melanomahereditary melanomagermline variantgenetic testgenestumor associations |
| spellingShingle | Chiara Anna Fiasconaro Alice Carbone Silvia Giordano Francesco Cavallo Paolo Fava Barbara Pasini Yuliya Yakymiv Sara Marchisio Pietro Quaglino Simone Ribero Gabriele Roccuzzo Germline Non-CDKN2A Variants in Melanoma and Associated Hereditary Cancer Syndromes Diseases melanoma hereditary melanoma germline variant genetic test genes tumor associations |
| title | Germline Non-CDKN2A Variants in Melanoma and Associated Hereditary Cancer Syndromes |
| title_full | Germline Non-CDKN2A Variants in Melanoma and Associated Hereditary Cancer Syndromes |
| title_fullStr | Germline Non-CDKN2A Variants in Melanoma and Associated Hereditary Cancer Syndromes |
| title_full_unstemmed | Germline Non-CDKN2A Variants in Melanoma and Associated Hereditary Cancer Syndromes |
| title_short | Germline Non-CDKN2A Variants in Melanoma and Associated Hereditary Cancer Syndromes |
| title_sort | germline non cdkn2a variants in melanoma and associated hereditary cancer syndromes |
| topic | melanoma hereditary melanoma germline variant genetic test genes tumor associations |
| url | https://www.mdpi.com/2079-9721/13/6/180 |
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