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Familial malignant melanoma

CDKN2A - Familial malignant melanoma

Most melanomas arise as a result of a combination of environmental and sporadic factors that cause mutations and are not part of a hereditary syndrome. However, about 10% of melanoma cases present with a positive family history which suggests that an inherited gene mutation, a shared environmental exposure, or both may be contributing to the risk for melanoma and other cancers. Individuals who have a strong family history of melanoma have a risk of developing melanoma that is 30-70 times higher than in the general population.

Clinical genetic testing is available for the primary known melanoma susceptibility gene, CDKN2A, which codes for the p16 protein (often referred to as p16 genetic testing). However, mutations in CDKN2A only account for approximately 10% of families with familial malignant melanoma, meaning that the cause of the familial melanoma remains unknown for most families. Mutations in CDKN2A have also been found in 8-16% of patients with multiple primary melanomas without a family history. Studies have suggested an increased risk for pancreatic cancer, ranging from 11% to 17%, in families with a CDKN2A/p16 gene mutation. The goal of cancer genetic testing is to identify high-risk patients so that prevention and early detection practices can be instituted before the development of malignancy. Studies have shown that reporting CDKN2A/p16 test results to high-risk patients significantly improves their compliance with early detection recommendations. Mutations in CDKN2A are inherited in an autosomal dominant manner, meaning each first degree relative (parent, child, and sibling) of an individual with this condition has a 50% chance of inheriting the disease causing mutation.


American Society of Clinical Oncology

Melanoma Research Foundation: