Non-invasive assessment of epidermal genomic markers of UV exposure in skin

The measurement of UV-induced DNA damage as a dosimeter of exposure and predictor of skin cancer risk has been proposed by multiple groups. While UV-induced mutations and adducts are present in normal-appearing UV-exposed epidermis, sampling normal non-lesional skin requires non-invasive methods to extract epidermal DNA for analysis. Here we demonstrate the feasibility of such an approach, termed Surfactant-based Tissue Acquisition for Molecular Profiling (STAMP). Sampling in patients was performed using a felt-tip pen soaked in a mixture of surfactants (Brij-30/DPS). 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 STAMP 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 vs. 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.