Ultradeep sequencing differentiates patterns of skin clonal mutations associated with sun-exposure status and skin cancer burden

Lei Wei, Sean R. Christensen, Megan E. Fitzgerald, James Graham, Nicholas D. Hutson, Chi Zhang, Ziyun Huang, Qiang Hu, Fenglin Zhan, Jun Xie, Jianmin Zhang, Song Liu, Eva Remenyik, Emese Gellen, Oscar R. Colegio, Michael Bax, Jinhui Xu, Haifan Lin, Wendy J. Huss, Barbara A. FosterGyorgy Paragh

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

In ultraviolet (UV) radiation–exposed skin, mutations fuel clonal cell growth. The relationship between UV exposure and the accumulation of clonal mutations (CMs) and the correlation between CMs and skin cancer risk are largely unexplored. We characterized 450 individual-matched sun-exposed (SE) and non-SE (NE) normal human skin samples. The number and relative contribution of CMs were significantly different between SE and NE areas. Furthermore, we identified hotspots in TP53, NOTCH1, and GRM3 where mutations were significantly associated with UV exposure. In the normal skin from patients with cutaneous squamous cell carcinoma, we found that the cancer burden was associated with the UV-induced mutations, with the difference mostly conferred by the low-frequency CMs. These findings provide previously unknown information on UV’s carcinogenic effect and pave the road for future development of quantitative assessment of subclinical UV damage and skin cancer risk.

Original languageEnglish (US)
Article numbereabd7703
JournalScience Advances
Volume7
Issue number1
DOIs
StatePublished - Jan 1 2021

ASJC Scopus subject areas

  • General

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