What are the genetic factors for melanoma

Researchers at Ohio State University have discovered a genetic cancer syndrome that predisposes certain people to developing eye melanoma, along with possible other types of cancer including lung, brain and other cancers.

The hereditary cancer syndrome is caused by inherited mutations in a gene called BAP1, the researchers said. The findings suggest that BAP1 mutations cause disease in a small percentage of patients with hereditary uveal melanoma and other cancers.

Uveal melanoma is a type of eye cancer that involves the iris, ciliary body, or choroid, which are collectively called the uvea. These tumors develop in the pigment cells, also called melanocytes, that are found in the uvea and give the eye its color. It is the most common eye tumor in adults.

The research results were published in the Journal of Medical Genetics.

"If we know a patient has this particular genetic mutation, we can be more proactive with increased cancer screening to try to detect these other potential cancers before they start to grow," said Mohamed H. Abdel-Rahman, MD, PhD, a researcher at Ohio State's Comprehensive Cancer Center, Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, the study's first author.

BAP1 appears to play an important role in regulating cell growth and proliferation, and loss of the gene helps lead to cancer, explained study leader Frederick H. Davidorf, MD, professor emeritus of ophthalmology at Ohio State.

"If our findings are validated, it would be good to monitor these patients to detect these cancers early when they are most treatable," said Davidorf, who treats eye tumor patients at Ohio State along with researcher Dr. Colleen Cebulla, a physician.

The study involved 53 unrelated uveal melanoma patients at high risk for hereditary cancer, as well as additional family members of one of the study participants. Of the 53 patients in the study, the researchers identified BAP1 germline variants in three patients.

"We don't yet know the exact pattern of susceptibility in these patients, and more research is needed," said Abdel-Rahman, associate professor in the divisions of human genetics and ophthalmology at the Ohio State University College of Medicine.

"So far, we have identified about six families with this inherited cancer syndrome. Together with researchers at Nationwide Children's Hospital, we are working to develop a clinical test to screen for mutations in the BAP1 gene," he said. "Families with this cancer syndrome should be screened for inherited mutations that increase their risk for several other cancers."

Other Ohio State researchers involved in the study were Robert Pilarski, James B. Massengill, Benjamin N. Christopher, Getachew Boru, and Peter Hovland of the Retina Associates in Denver, Colorado.

The research was funded by a Patti Blow Research Foundation Ophthalmology Grant. The American Cancer Society also supported the research.