A new clue comes from scientists at the University of North Carolina at Chapel Hill Schools of Medicine and Public Health. Their research indicates that early life sun exposure, from birth to 20 years old, may specifically increase the risk of melanomas with BRAF gene mutations. A different mutation, on the NRAS gene, was found in patients who had sun exposure later in life (between ages 50 to 60 years old). The results indicate that different subtypes of melanoma are associated with different risk factors

"The findings suggest that melanoma subtypes have different causes. This is important for learning more about how to prevent and treat skin cancer," said Dr. Nancy Thomas, associate professor of dermatology in the UNC School of Medicine, a member of the UNC Lineberger Comprehensive Cancer Center and lead author of the study. This finding is expected to strengthen current recommendations to protect children from sun exposure in order to prevent melanoma, Thomas said.

The study, published in the May 2007 edition of the journal Cancer Epidemiology Biomarkers and Prevention, presents some of the first data to link early life sunlight exposure to a specific mutation in melanomas.

Researchers interviewed 214 melanoma patients in North Carolina about their risk factors for melanoma and about the various places they had lived. Each patient's UV sun exposure was estimated from their residential history and satellite-base measurements. DNA from the patients' melanomas was then analyzed for mutations.

Patients with melanomas that contained the BRAF mutation, found in about half of all melanomas, were more likely to report high levels of sun exposure before age 20. People with the NRAS mutation were more likely to have had high exposure between the ages of 50 and 60. About 15 percent of melanomas contain the NRAS mutation.

The findings come from the initial phase of an ongoing study that will ultimately include more than 1,000 patients from the U.S. and Australia. The research was funded by the Dermatology Foundation, the National Cancer Institute and the UNC Lineberger Cancer Center.

med.unc

The researchers systematically examined gene expression patterns in the endothelial cells that line blood vessels derived from normal resting tissues, regenerating tissues, and tumors. A comparison of the normal vessels revealed several organ-specific endothelial genes that could potentially aid in the delivery of molecular medicine to specific anatomical sites. The study also revealed 13 genes that are selectively overexpressed in tumor blood vessels. Although the function of most of the newly identified genes in tumor blood vessels is unclear, many of the genes encode cell surface proteins, making them appealing targets for the development of new therapeutic agents.

One of the cell surface proteins identified, called CD276, was found to be frequently overexpressed in the blood vessels of a variety of human cancers. The researchers also report that in many of the tumors examined CD276 was also overexpressed by the tumor cells, making this protein a particularly attractive target because a suitable inhibitory molecule might be able to deliver a double blow: one to the tumor cells themselves and the other to the blood vessels that feed it. "These studies reveal that tumor vessels contain a unique molecular fingerprint that can be used to distinguish them from normal proliferating vessels," explained Dr. St. Croix; they also provide new targets that could help guide the development of safer vascular-targeted therapies with potentially fewer side effects."

cellpress