Gene Linking Hereditary Predisposition to Melanoma, Future Genetic Screening Test

EMBARGOED UNTIL MARCH 20, 1999

GENE LINKING HEREDITARY PREDISPOSITION TO MELANOMA COULD HOLD THE KEY TO FUTURE GENETIC SCREENING TEST

NEW ORLEANS (March 20, 1999) - Genetic susceptibility has long been recognized as a risk factor in the development of several types of cancer, including melanoma. Emerging research establishing the significance of a gene in hereditary melanoma could improve the diagnosis of this deadliest form of skin cancer for patients with a family history of melanoma.

Speaking today at the American Academy of Dermatology's 57th Annual Meeting in New Orleans, dermatologist Michael Piepkorn, MD, PhD, Professor, Division of Dermatology, University of Washington, Seattle, discussed the importance of the isolation of a melanoma susceptibility gene, p16, in future detection of the disease.

"Scientific interest in familial melanoma and the related condition of the atypical nevus syndrome - which are unusual moles that are generally larger and occur in greater number than normal moles, vary in color, and often have irregular borders - led to the mapping of a major melanoma susceptibility region to human chromosome 9," said Dr. Piepkorn. "This advance allowed the cloning and isolation of the candidate melanoma susceptibility gene in 1994, which is now most commonly referred to as p16."

Approximately 10 percent of patients with melanoma will have one or more first-degree relatives, such as a parent, sibling or child, who are also afflicted with the disease. The association between melanoma and heredity indicates a genetic abnormality in the germline - an inherited gene that is passed through successive generations, resulting in a tendency toward developing a disease such as melanoma.

In the remaining 90 percent of melanoma cases that are not influenced by heredity, p16 may still be involved due to random or spontaneous changes in the gene from mutations or environmental factors such as ultraviolet light (UV).

The protein product of p16 acts as a classical tumor suppressor, limiting the growth and new formation of developing tumor cells. When the gene carries a mutation, the protein product is either partially or completely nonfunctional. Dr. Piepkorn explained that the current scientific evidence indicates that this effect leads to a susceptibility to melanoma. The risk of melanoma in gene carriers appears to be influenced by environmental factors, especially UV light from sun exposure.
"The isolation and identification of p16 opens the door for the possibility of developing a reliable genetic screening test to assess future melanoma risk in patients who have either had previous melanomas or a family history of melanoma," said Dr. Piepkorn. "What we're hoping is that in the next few years, we can determine whether or not these patients are at risk of developing melanoma simply by testing for mutations in p16."

Dr. Piepkorn explained that the genetic screening test would be a blood test that looks for mutations in the p16 gene by analyzing DNA from the patient's white blood cells. If mutations in the melanoma susceptibility gene are identified, a patient has a better than 50 percent chance of developing melanoma in his or her lifetime.

"By identifying patients that are genetically at risk for developing melanoma, dermatologists will be able to perform careful screenings on these patients on a regular basis to detect early signs of melanoma," said Dr. Piepkorn.

When detected early, surgical removal of thin melanomas can cure the disease in most cases. However, early detection is essential - there is a direct correlation between the thickness of the melanoma and survival rate. The American Academy of Dermatology advises everyone to examine their skin regularly to detect changes in its appearance, especially changes in existing moles or blemishes.
The overall incidence of melanoma is rising at an alarming rate. An estimated 44,200 new cases of malignant melanoma are expected to be diagnosed in the United States in 1999, a 6 percent increase from 1998. Six out of seven skin cancer deaths are from malignant melanoma.

The American Academy of Dermatology, founded in 1938, is the largest, most influential, and most representative of all dermatologic associations. With a membership over 11,000 dermatologists worldwide, the Academy is committed to: advancing the science and art of medicine and surgery related to the skin; advocating high standards in clinical practice, education, and research in dermatology; supporting and enhancing patient care; and promoting a lifetime of healthier skin, hair, and nails. For more information, contact the AAD at 1-888-462-DERM or www.aad.org.

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