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  • Ultradeep sequencing differentiates patterns of skin clonal mutations associated with sun-exposure status and skin cancer burden
Title: Ultradeep sequencing differentiates patterns of skin clonal mutations associated with sun-exposure status and skin cancer burden
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.  more » « less
Award ID(s):
1910492 1716400
PAR ID:
10290004
Author(s) / Creator(s):
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; more » ; « less
Date Published:
Journal Name:
Science Advances
Volume:
7
Issue:
1
ISSN:
2375-2548
Page Range / eLocation ID:
eabd7703
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
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