Title: Noninvasive Assessment of Epidermal Genomic Markers of UV Exposure in Skin.
Authors: Muradova, Elnara; Patel, Nishit; Sell, Brittney; Bittencourt, Bruna B; Ojeda, Sandra S; Adelmann, Charles H; Cen, Ling; Cheng, Chia-Ho; Shen, Jianjun; Davis, Christel M; Ehli, Erik A; Newberg, Justin Y; Cherpelis, Basil; Black, Michael A; Mann, Michael B; Mitragotri, Samir; Tsai, Kenneth Y
Published In J Invest Dermatol, (2021 01)
Abstract: The measurement of UV-induced DNA damage as a dosimeter of exposure and predictor of skin cancer risk has been proposed by multiple groups. Although UV-induced mutations and adducts are present in normal-appearing UV-exposed epidermis, sampling normal nonlesional skin requires noninvasive methods to extract epidermal DNA for analysis. Here, we demonstrate the feasibility of such an approach, termed surfactant-based tissue acquisition for molecular profiling. Sampling in patients was performed using a felt-tip pen soaked in a mixture of surfactants (Brij-30/N-decyl-N,N-dimethyl-3-ammonio-1-propanesulfonate). In mice, we show that the epidermis can be selectively removed without scarring, with complete healing within 2 weeks. We exposed hairless mice to low-dose UV radiation over a period of 3 months and serially sampled them through up to 2 months following the cessation of UV exposure, observing a progressive increase in a UV signature mutational burden. To test whether surfactant-based tissue acquisition for molecular profiling could be applied to human patients, samples were collected from sun-exposed and sun-protected areas, which were then subjected to high-depth targeted exome sequencing. Extensive UV-driven mosaicism and substantially increased mutational loads in sun-exposed versus sun-protected areas were observed, suggesting that genomic measures, as an integrated readout of DNA damage, repair, and clonal expansion, may be informative markers of UV exposure.
PubMed ID: 32553564
MeSH Terms: Animals; DNA Damage; Epidermis/metabolism*; Epidermis/pathology; Epidermis/radiation effects; Genetic Markers/genetics*; Genomics/methods*; Humans; Skin Neoplasms/genetics*; Skin Neoplasms/metabolism; Skin Neoplasms/pathology; Ultraviolet Rays/adverse effects*