Study Reveals Source of DNA Mutations in Melanoma

The mutations that give rise to melanoma result mainly from a chemical conversion in DNA fueled by sunlight--not just a DNA copying error as previously believed, reports a study by Van Andel Institute scientists published in the July 30, 2021 issue of Science Advances. The open-access article is titled “The Major Mechanism of Melanoma Mutations Is Based on Deamination of Cytosine in Pyrimidine Dimers As Determined by Circle Damage Sequencing.” The findings upend long-held beliefs about the mechanisms underlying the disease, reinforce the importance of prevention efforts, and offer a path forward for investigating the origins of other cancer types.  “Cancers result from DNA mutations that allow defective cells to survive and invade other tissues. However, in most cases, the source of these mutations is not clear, which complicates development of therapies and prevention methods,” said Gerd Pfeifer, PhD, a VAI professor and the study’s corresponding author. “In melanoma, we’ve now shown that damage from sunlight primes the DNA by creating ‘premutations’ that then give way to full mutations during DNA replication.”
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