@article{07aad4acc68b46e282d90b2b674bfcbd,
title = "Ultradeep sequencing differentiates patterns of skin clonal mutations associated with sun-exposure status and skin cancer burden",
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{\textquoteright}s carcinogenic effect and pave the road for future development of quantitative assessment of subclinical UV damage and skin cancer risk.",
author = "Lei Wei and Christensen, {Sean R.} and Fitzgerald, {Megan E.} and James Graham and Hutson, {Nicholas D.} and Chi Zhang and Ziyun Huang and Qiang Hu and Fenglin Zhan and Jun Xie and Jianmin Zhang and Song Liu and Eva Remenyik and Emese Gellen and Colegio, {Oscar R.} and Michael Bax and Jinhui Xu and Haifan Lin and Huss, {Wendy J.} and Foster, {Barbara A.} and Gyorgy Paragh",
note = "Funding Information: This work was mainly supported by the Roswell Park Alliance Foundation. L.W. and S.L. were supported, in part, by NIH grant U24CA232979. The used Genomics and Bioinformatics Shared Resources and Rapid Tissue Acquisition Program at Roswell Park Comprehensive Cancer Center was supported by NCI grant P30CA016056. L.W. and J.X. were supported, in part, by a travel grant from NIH 5U24ES026465. S.R.C. was supported by a Career Development Award from the Dermatology Foundation. Publisher Copyright: Copyright {\textcopyright} 2021 The Authors, some rights reserved.",
year = "2021",
month = jan,
day = "1",
doi = "10.1126/sciadv.abd7703",
language = "English (US)",
volume = "7",
journal = "Science advances",
issn = "2375-2548",
publisher = "American Association for the Advancement of Science",
number = "1",
}