Germline mutations predisposing to melanoma and associated malignancies and syndromes: a narrative review

The pathogenesis of melanoma is influenced by a complex combination of environmental factors and individual genetic susceptibility. Familial melanoma refers to cases where there are two first-degree relatives with a melanoma diagnosis. Less strict definitions include second-degree relatives or even three or more of any degree from the same family, although this is not clearly defined in the literature. The term hereditary melanoma is reserved for sporadic or familial melanomas linked to high-risk genes with high penetrance. The first genes related to melanoma were CDKN2A and CDK4, but recently, other genes, mostly tumor suppressor genes, have been described. Internal malignancies, particularly pancreatic cancer, have also been associated with melanoma. Recent studies suggest that there could be a link between melanoma and other neoplasms and tumor predisposition syndromes. This review presents an updated overview of familial melanoma criteria and genes involved in melanoma pathogenesis, emphasizing their clinicopathological aspects and other associated malignancies.