A new study looking at the genomic landscape of individual melanocytes from human skin had found that risk for melanoma may be estimated long before detection of any suspicious moles.1
Researchers collected normal skin from 19 sites across 6 patient donors. Skin was biopsied from 4 cadavers with no history of skin cancer, and 2 melanoma survivors. All were light skin tone. They sequenced melanocyte DNA in these samples, 1 cell at a time to count mutations, with an emphasis of mutations that are the main drivers of melanoma.
They found an average mutation burden of 7.9 mutations per megabase. Mutation burdens on melanocytes varied by anatomic site. For example, sun-shielded sites had fewer mutations than sun-exposed sites.
Additionally, they found that melanocytes from normal skin near a melanoma in the samples from patients with cancer had more mutations, including melanoma-associated mutations, than skin from the same sites in samples taken from the cadavers.
People with many moles should still be screened, according to A. Hunter Shain, PhD, assistant professor in UCSF’s Department of Dermatology, but only 30% of melanomas arise from preexisting moles.
“Melanomas really can appear out of nowhere,” Dr Shain said in a press release. “We found out in this work that normal skin contains numerous melanocytes that already exhibit some of the mutations associated with cancer. Essentially, we found the precursors to the 70 percent of melanomas that do not arise from pre-existing moles.”
Because there is so little DNA in a single cell compared to a typical biological specimen containing a multitude of cells, the DNA must be amplified to obtain sufficient amounts. The enzymes used to amplify DNA introduce errors, but Dr Shain’s team used additional lab methods to better distinguish amplification mistakes from true mutations, and developed computer algorithms to further enhance accuracy of the analysis.
Tang J, Fewing E, Chang D, et al. The genomic landscapes of individual melanocytes from human skin. Nature. Published October 7, 2020. doi:10.1038/s41586-020-2785-8.