NEW BRUNSWICK/PISCATAWAY, N.J. — Rutgers Associate Professor Suzie Chen has discovered a gene responsible for melanoma, the most aggressive form of malignant skin cancer. A paper describing the research by Chen and her colleagues at the National Human Genome Research Institute will be published online by Nature Genetics on April 21, and will appear subsequently in a print issue of the journal.
Melanoma may appear in places that never see sun, spread to other parts of the body and become lethal. This type of cancer is not generally responsive to chemotherapy. According to a report from the National Cancer Institute, in the United States the incidence rate of melanoma has more than doubled in the past 20 years.
Chen has been on the track of this gene since her 1995 arrival at Rutgers, The State University of New Jersey. Her research was conducted in the Susan Lehman Cullman Laboratory for Cancer Research at Rutgers’ Ernest Mario School of Pharmacy.
“I did not set out to do a melanoma study,” said Chen. “All my life I have been interested in cell transformation and differentiation. In this case, I was investigating how a fat cell becomes a fat cell when I observed that one of the mice in my experiment developed pigmented tumors. Upon further characterization, these tumors were confirmed to be melanoma.
“After many years of work, we identified a gene that was involved in these skin abnormalities and went on to prove that it indeed causes melanoma in the mouse system,” said Chen.
Surprisingly, the gene is not a known oncogene – one known to cause cancer – but one whose normal functions are in the brain.
Chen explained that the expression of a given gene, whether it is turned on or off, or when, is tightly regulated by many factors. “It is only in a melanocyte skin cell when the expression of this particular gene is turned on that it leads to the development of melanoma,” said Chen. “While in the brain, where it is expressed normally, its functions are associated with learning and memory.”
Chen and her collaborators took the next step in this scientific investigation using human biopsy tissues with various stages of melanoma. In more than one third of these human samples, they detected signs of the same aberrant gene expression seen in the laboratory animals that had melanoma. This confirmed that the gene involved in melanoma development in the mice is also implicated in some human melanomas. While there are typically many paths leading to cancer development, this is a breakthrough in pinpointing one of them that occurs in both animals and humans.
“We hope to use this knowledge we’ve gained to investigate better ways of treating the disease. Early detection is key in treating melanoma, but malignant melanoma does not normally respond well to conventional chemotherapy,” said Chen. “We need to find more effective ways to treat the disease. The biggest problem we have is our inability to target the tumor cells. Most of the treatments available today affect normal cells, as well. With our understanding of at least one genetic factor in melanoma, we may now have the ability to design a new, more specific drug to target that gene or the protein it expresses,” she concluded.