Details

Autor(en) / Beteiligte

• 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.

Titel

Noninvasive Assessment of Epidermal Genomic Markers of UV Exposure in Skin

Ist Teil von

• Journal of investigative dermatology, 2021-01, Vol.141 (1), p.124-131.e2

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2021

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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.