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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...

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Autores principales: Wei, Lei, Christensen, Sean R., Fitzgerald, Megan E., Graham, James, Hutson, Nicholas D., Zhang, Chi, Huang, Ziyun, Hu, Qiang, Zhan, Fenglin, Xie, Jun, Zhang, Jianmin, Liu, Song, Remenyik, Eva, Gellen, Emese, Colegio, Oscar R., Bax, Michael, Xu, Jinhui, Lin, Haifan, Huss, Wendy J., Foster, Barbara A., Paragh, Gyorgy
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Association for the Advancement of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775785/
https://www.ncbi.nlm.nih.gov/pubmed/33523857
http://dx.doi.org/10.1126/sciadv.abd7703
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author Wei, Lei
Christensen, Sean R.
Fitzgerald, Megan E.
Graham, James
Hutson, Nicholas D.
Zhang, Chi
Huang, Ziyun
Hu, Qiang
Zhan, Fenglin
Xie, Jun
Zhang, Jianmin
Liu, Song
Remenyik, Eva
Gellen, Emese
Colegio, Oscar R.
Bax, Michael
Xu, Jinhui
Lin, Haifan
Huss, Wendy J.
Foster, Barbara A.
Paragh, Gyorgy
author_facet Wei, Lei
Christensen, Sean R.
Fitzgerald, Megan E.
Graham, James
Hutson, Nicholas D.
Zhang, Chi
Huang, Ziyun
Hu, Qiang
Zhan, Fenglin
Xie, Jun
Zhang, Jianmin
Liu, Song
Remenyik, Eva
Gellen, Emese
Colegio, Oscar R.
Bax, Michael
Xu, Jinhui
Lin, Haifan
Huss, Wendy J.
Foster, Barbara A.
Paragh, Gyorgy
author_sort Wei, Lei
collection PubMed
description 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.
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spelling pubmed-77757852021-01-14 Ultradeep sequencing differentiates patterns of skin clonal mutations associated with sun-exposure status and skin cancer burden Wei, Lei Christensen, Sean R. Fitzgerald, Megan E. Graham, James Hutson, Nicholas D. Zhang, Chi Huang, Ziyun Hu, Qiang Zhan, Fenglin Xie, Jun Zhang, Jianmin Liu, Song Remenyik, Eva Gellen, Emese Colegio, Oscar R. Bax, Michael Xu, Jinhui Lin, Haifan Huss, Wendy J. Foster, Barbara A. Paragh, Gyorgy Sci Adv Research Articles 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. American Association for the Advancement of Science 2021-01-01 /pmc/articles/PMC7775785/ /pubmed/33523857 http://dx.doi.org/10.1126/sciadv.abd7703 Text en Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). https://creativecommons.org/licenses/by-nc/4.0/ https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (https://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.
spellingShingle Research Articles
Wei, Lei
Christensen, Sean R.
Fitzgerald, Megan E.
Graham, James
Hutson, Nicholas D.
Zhang, Chi
Huang, Ziyun
Hu, Qiang
Zhan, Fenglin
Xie, Jun
Zhang, Jianmin
Liu, Song
Remenyik, Eva
Gellen, Emese
Colegio, Oscar R.
Bax, Michael
Xu, Jinhui
Lin, Haifan
Huss, Wendy J.
Foster, Barbara A.
Paragh, Gyorgy
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
title_full Ultradeep sequencing differentiates patterns of skin clonal mutations associated with sun-exposure status and skin cancer burden
title_fullStr Ultradeep sequencing differentiates patterns of skin clonal mutations associated with sun-exposure status and skin cancer burden
title_full_unstemmed Ultradeep sequencing differentiates patterns of skin clonal mutations associated with sun-exposure status and skin cancer burden
title_short Ultradeep sequencing differentiates patterns of skin clonal mutations associated with sun-exposure status and skin cancer burden
title_sort ultradeep sequencing differentiates patterns of skin clonal mutations associated with sun-exposure status and skin cancer burden
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7775785/
https://www.ncbi.nlm.nih.gov/pubmed/33523857
http://dx.doi.org/10.1126/sciadv.abd7703
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