Yale researchers working as part of an international team have isolated the gene for the most common form of human cancer, basal cell carcinoma of the skin.
Their findings, published in the June 14 issue of the journal Cell, could lead to a skin creme that would cure the disease and to genetic testing for susceptibility to skin cancer.
The new gene, called PTC, is essential for keeping skin cells under control. "Genetic mutation of PTC is the key step in development of skin cancer," says Dr. Allen Bale, senior author of the Cell article and director of the Cancer Genetics Program at the Yale Cancer Center.
The team's search for the gene began with studies of a rare hereditary disorder called nevoid basal cell carcinoma syndrome NBCCS . People with the disorder develop thousands of skin cancers and may also have birth defects and childhood brain tumors. In 1992 Dr. Bale mapped the NBCCS gene to human chromosome 9, and over the past four years he and his collaborators sorted through 40 genes from this region. Last month, Dr. Bale's group reported isolation of PTC, a human gene similar to a previously reported fruit fly gene, which is called a "patched" gene because it causes abnormal patches on the flies.
"Nobody had a clue that this gene had anything to do with human cancer, but some of the features in fruit flies were strangely similar to birth defects in NBCCS," Dr. Bale says. The researchers discovered that individuals with NBCCS are born with a mutation of PTC in all of their cells. Further investigation revealed the same mutation in people with noninherited basal cell carcinomas. Approximately one million cases of basal cell carcinoma occur each year, often caused by overexposure to sunlight.
The discovery paves the way for novel approaches to preventing and treating basal cell carcinoma, according to Dr. David J. Leffel, associate professor of dermatology at the School of Medicine and a coauthor of the report. "Although still several years away, it's not unreasonable to imagine an ointment that, when applied to the skin, may control the growth of this cancer," he says. "Because skin cancers occur externally rather than in internal organs, a dose of a medication that can replace the function of the faulty gene could be applied directly to the cancer while minimizing side effects."
In addition, since individuals may be genetically predisposed to skin cancers that are much milder than NBCCS, Dr. Bale and his colleagues suggest that those who have had more than two basal cell carcinomas be screened to determine if they are genetically predisposed to the cancer. "Through a simple blood test, we can identify people who are cancer-prone," he explains. "For those who are, more aggressive monitoring and preventive measures such as staying out of the sun and using sunscreen can be applied."
Also collaborating on the study were Michael Dean from the National Cancer Institute in Frederick, Maryland; Brandon Wainwright and Georgia Chenevix-Trench from the University of Queensland and the Queensland Institute of Medical Research in Brisbane, Australia; and Rune Toftgard from the Karolinska Institute in Huddinge, Sweden.