Biomarker test shows promise for melanoma diagnosis

DNA methylation is the modification of a strand of DNA in a way that alters gene expression, the means by which coded information in a gene is converted for use in cells.

In an accepted paper published online Jan. 21 in the journal Pigment Cell & Melanoma Research, a team of UNC researchers led by Kathleen Conway Dorsey, PhD, research assistant professor of epidemiology at UNC Gillings School of Global Public Health, tested whether DNA methylation profiling could be accomplished on melanoma and mole tissues that had been preserved in fixatives for typical pathology examination after biopsy. They found that results on tissues prepared in this way were reliable and that DNA methylation distinguished malignant melanomas from non-malignant moles.

Melanoma is one of the only forms of cancer that is still on the rise and is the most common form of cancer in young adults. The incidence of melanoma in women under age 30 has increased more than 50 percent since 1980.

“When melanoma is diagnosed early, the prognosis is good,” said Nancy Thomas, MD, PhD, professor of dermatology and member of UNC Lineberger Comprehensive Cancer Center. “However, once it spreads, it is very difficult to treat. Melanomas and moles can appear similar on the skin and under the microscope making diagnosis of some melanomas difficult. That’s why we wanted to determine whether a test for DNA methylation is feasible as a tool for diagnosis.”

“We are very excited because, with this study, we have shown that this type of testing is feasible and that it has the potential to reliably distinguish between melanoma and benign skin lesions,” said Dorsey, who is also a member of UNC Lineberger Comprehensive Cancer Center. “Devising a molecular test that could aid in the early specific diagnosis of melanoma could have significant benefit for patients.”

The team’s research pinpointed sites on 22 genes that have significantly different methylation levels between melanomas and non-melanoma lesions, as well as 12 locations that are highly predictive of melanoma. According to Thomas, another goal of the team is to develop a DNA-methylation test for melanoma tumor DNA that is shed into the bloodstream and that can serve as a measure for disease activity.

“If this test can be developed, it opens the door to diagnose recurrence early and initiate treatment while tumors are more likely to respond to treatment. It would also give us another way to monitor patients for response to treatment and help us better optimize treatments for each patient,” Thomas noted.

Other members of the UNC research team include Sharon Edmiston, BS, research specialist at the cancer center; Zakaria Khondker, doctoral student, biostatistics; Pamela Groben, MD, clinical professor, pathology and laboratory medicine; Xin Zhou, PhD, research assistant, biostatistics; Pei Fen Kuan, PhD, research assistant professor, biostatistics, Honglin Hao, research specialist, dermatology; Craig Carson, PhD, postdoctoral student, toxicology; and David Ollila, MD, associate professor, surgery.

The team also included Haitao Chu, MD, PhD, of the University of Minnesota, and Marianne Berwick, PhD, MPH, of the University of New Mexico.

The article, “DNA Methylation Profiling Distinguishes Malignant Melanomas from Benign Nevi,” is available on the journal’s website.

Research was funded by the National Cancer Institute and a UNC Lineberger Pilot Grant.

UNC Gillings School of Global Public Health contact: Ramona DuBose, director of communications, (919) 966-7467 or ramona_dubose@unc.edu.