Melanoma is a malignancy that arises from melanocytes of the skin. Approximately 59,000 cases of melanoma occur in the U.S. each year and the incidence of this cancer is increasing.³⁷ Approximately ten percent of all melanoma cases are hereditary. There is also a strong link to development of pancreatic cancer in melanoma families.

Research by family linkage studies identified an autosomal-dominant, melanoma gene located on chromosome 9p21.⁴⁰ This gene, called p16 (also known as CDKN2A or INK4A or MTS1), accounts for up to 40 percent of these hereditary melanoma cases. p16 is a tumor suppressor gene involved in regulation of cell growth. p16 regulates cell proliferation by inhibiting the CDK4 cell cycle protein kinase; thus, mutations in p16 that disrupt function lead to unregulated cell growth.

Cloning of the p16 gene indicated that it is composed of three exons (471 base pair) encoding a 156 amino acid protein. At present about 50 unique germline mutations have been reported in families with melanoma and pancreatic cancer. Mutations are found to occur within the coding sequence, splicing, and promoter regions of the gene. In the U.S., p16 mutations are likely responsible for 1000-2000 new melanoma cases each year. Mutations in the p16 gene account for the majority of known genetic causes of inherited melanoma cases. Other genes such as CDK4 and p14ARF account for a handful (<1%) of other melanoma cases.

» Identifying Patients at Risk for Melanoma

A genetic test for hereditary melanoma