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Publication : Noninvasive Assessment of Epidermal Genomic Markers of UV Exposure in Skin.

First Author  Muradova E Year  2021
Journal  J Invest Dermatol Volume  141
Issue  1 Pages  124-131.e2
PubMed ID  32553564 Mgi Jnum  J:300331
Mgi Id  MGI:6491518 Doi  10.1016/j.jid.2020.05.093
Citation  Muradova E, et al. (2021) Noninvasive Assessment of Epidermal Genomic Markers of UV Exposure in Skin. J Invest Dermatol 141(1):124-131.e2
abstractText  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.
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