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A gene known to be mutated in many different cancers, but thought to be relatively unimportant in melanoma, may be a key indicator of how the disease will respond to radiation therapy and whether it will spread.

A UNC-led team reported their laboratory findings in the April 27, 2012 online edition of Pigment Cell & Melanoma Research.

William Kaufmann, PhD, professor of pathology and laboratory medicine and senior study author, explains, “p53 is the most commonly mutated gene in cancer. What’s unusual in melanoma is that it’s not commonly mutated and was therefore thought unimportant. But when we investigated p53 signaling function in melanoma, we discovered that it is dysfunctional in lots of melanoma.

“Cells that have defective signaling pathways have different gene expression patterns than cells that have effective signaling pathways. Using microarray technology, we developed a method to estimate p53 signaling function in melanomas by looking at specific patterns in gene expression. We found that the distinct patterns predicted the development of distant metastases in patients with melanoma and decreased sensitivity of melanoma cells to radiation therapy.

“Our finding has clinical implications that should be further explored. For the vast majority of primary melanomas, general surgical excision is curative.

What makes melanoma problematic is that even a small primary melanoma can recur later in a distant lymph node or become metastatic. Metastatic melanoma is very hard to treat.”

“If we could better identify primary tumors that are likely to have metastasized at the time of surgery or have increased probability of metastasizing later, we might be able to include post-surgery adjuvant therapy before metastasis arises.”

“Our next step is to complete additional, larger pre-clinical studies,” he adds. Dr. Kaufmann is a member of UNC Lineberger Comprehensive Cancer Center.

Funding for the research was provided by National Institutes of Health Public Health Service grants.

UNC authors were: Craig Carson, PhD; Yingchun Zhou, BS; Maria Sambade, PhD; Eldon Peters, BS; Patrick Tompkins, BS; Dennis Simpson, PhD; Nancy Thomas, MD, PhD; Cheng Fan, MS; Janiel Shields, PhD; and Joseph Ibrahim, PhD.

Additional authors are from the University of South Carolina Upstate in Spartanburg, South Carolina, the University of Minnesota, and the Institut Gustave Roussy in Villejuif, France.