A genetic test for hereditary melanoma
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
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
melanoma cases. p16 is
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