A critical link in mapping recurrent mutations of melanoma has been discovered by researchers at Washington State University (WSU) School of Molecular Biosciences (SMB), a part of the university’s College of Veterinary Medicine. The study, which was conducted in collaboration with researchers at Georgia State University, could lead to a better understanding of which mutations are important for causing skin cancer in humans and potentially identify new drug targets for treatment.
In a paper published last week in “Nature Communications,” the research team established that DNA binding by a specific set of transcription factors, called ETS, is inherently mutagenic in UV-exposed cells. With new genome mapping technology, these findings provide a crucial understanding of mutations that result at ETS binding sites located in specific genes that are known to be drivers in the onset of melanoma in humans.
Using a WSU-established sequencing-based technology that allows the mapping of the locations of UV-induced DNA damage throughout the whole human genome, researchers generated a high-resolution UV damage map in human cells. By correlating the UV damage map with melanoma mutations, they discovered significantly elevated UV damage levels at ETS binding sites, which significantly increased mutation rates at the same sites in sequenced melanoma genomes.
“UV-induced DNA damage is the major risk factor for melanoma, and DNA repair is a vital first line of defense against DNA damage to prevent mutations and cancer,” said Steven Roberts, Ph.D., assistant professor at WSU’s SMB. “These pivotal results establish a fundamental research tool in cancer research and confirm we are on the correct course to further discovery by mapping UV damage in human cells.”