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Skin damage from UV light seen in sun-shielded skin

PLOS Genetics
Reuters Health - 18/01/2021 - UV light-related skin damage is common even in skin cells typically shielded from the sun, regardless of a person's age, whereas endogenous DNA skin damage - from metabolic byproducts - accumulates over time, a sequencing study reveals.

"Baseline levels of genome changes in skin defined by our study will help us and other researchers to identify gene variants resulting in higher, potentially disease-prone levels of genome instability in individuals recruited from the NIEHS Environmental Polymorphisms Registry (EPR; https://bit.ly/2KqkqU6), " Dr. Dmitry Gordenin of the U.S. National Institute of Environmental Health Sciences in Research Triangle Park, North Carolina told Reuters Health by email.

"Ongoing whole-genome sequencing of thousands of EPR DNAs," he said, "will allow us to limit recruitment and somatic clone sequencing to individuals that carry variants of unknown significance in genes with known roles in preventing genome instability."

As reported in PLOS Genetics, Dr. Gordenin and colleagues sequenced genomes of single cell-derived clonal lineages (i.e., cells expanded in the laboratory) obtained from primary skin cells of healthy individuals. The cohort included five African American and 16 White donors, allowing the team to assess whether the accumulation of somatic genome changes is different between the two races.

Among the findings:

- Each skin cell carries from 402 to 14,029 base substitutions, seven to 71 indels (insertions/deletions of bases in a genome) and one to 14 structural variants per cell.

- Mutation burden in healthy skin cells was similar to the median mutation load in cancers.

- Total base substitutions in samples from White donors were higher (median 1,824) than in the skin fibroblasts and melanocytes from Black donors (median 715).

- UV-induced base substitutions, insertions and deletions are prominent even in sun-shielded skin.

- Accumulation of mutations due to spontaneous deamination of methylated cytosines was detected, as well as insertions and deletions characteristic of DNA replication errors in these cells; these endogenously induced somatic mutations and indels show a linear increase with age, while UV-induced mutation load is age independent.

Overall, the authors say, "somatic mutations in skin of healthy individuals reflect the interplay of environmental and endogenous factors in facilitating genome instability and carcinogenesis."

Coauthor Dr. Natalie Saini, of the Medical University of South Carolina in Charleston, told Reuters Health by email, "Baseline levels of genome changes in skin defined by our study may help researchers to develop testing procedures for detecting high, and potentially disease-prone, levels in otherwise healthy individuals."

"We plan to adapt our technology and analytical pipeline to accurately measure across the entire genome the load with mutations caused by DNA-damaging chemicals that can be present in the environment to understand how cells across human bodies accumulate genome instability over a person's lifetime," she added.

Dr. Hensin Tsao, Head, Skin Cancer Genetics Laboratory/Wellman Center for Photomedicine and Director of the MGH Melanoma and Pigmented Lesion Center and the DMGH Melanoma Genetics Program in Boston, commented by phone to Reuters Health. He noted that a 2015 study led by the Sanger Institute and published in Science "used blepharoplasty tissue - i.e., real skin. The skin looked completely normal, and the authors sequenced little bits of those cells and found about 140 driver mutations per square centimeter sitting in that real skin." (https://bit.ly/2XOBciW)

"By contrast, for the current study, they took cells off the biopsy and grew them up in culture to one million, so the only cells surviving for analysis were those that were fit enough to survive," he said. "This is not an accurate reflection of skin. They are taking cells that can expand and grow, but we don't know if these are actually the predominant cell type in the skin."

Clinically, he said, the study "confirmed on a genetic level what's well known: that UV light is attenuated by melanin. For clinicians who argue there is no good evidence that UV causes melanoma, we see that there's clearly an age-dependent increase in the amount of UV damage and a color-associated protection against these mutations; therefore, UV is contributing to skin cancer on normal skin."

SOURCE: https://bit.ly/3oVR7YJ PLOS Genetics, online January 14, 2021

By Marilynn Larkin

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