Cargando…
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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1783630544225959936 |
---|---|
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. |
format | Online Article Text |
id | pubmed-7775785 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT weilei ultradeepsequencingdifferentiatespatternsofskinclonalmutationsassociatedwithsunexposurestatusandskincancerburden AT christensenseanr ultradeepsequencingdifferentiatespatternsofskinclonalmutationsassociatedwithsunexposurestatusandskincancerburden AT fitzgeraldmegane ultradeepsequencingdifferentiatespatternsofskinclonalmutationsassociatedwithsunexposurestatusandskincancerburden AT grahamjames ultradeepsequencingdifferentiatespatternsofskinclonalmutationsassociatedwithsunexposurestatusandskincancerburden AT hutsonnicholasd ultradeepsequencingdifferentiatespatternsofskinclonalmutationsassociatedwithsunexposurestatusandskincancerburden AT zhangchi ultradeepsequencingdifferentiatespatternsofskinclonalmutationsassociatedwithsunexposurestatusandskincancerburden AT huangziyun ultradeepsequencingdifferentiatespatternsofskinclonalmutationsassociatedwithsunexposurestatusandskincancerburden AT huqiang ultradeepsequencingdifferentiatespatternsofskinclonalmutationsassociatedwithsunexposurestatusandskincancerburden AT zhanfenglin ultradeepsequencingdifferentiatespatternsofskinclonalmutationsassociatedwithsunexposurestatusandskincancerburden AT xiejun ultradeepsequencingdifferentiatespatternsofskinclonalmutationsassociatedwithsunexposurestatusandskincancerburden AT zhangjianmin ultradeepsequencingdifferentiatespatternsofskinclonalmutationsassociatedwithsunexposurestatusandskincancerburden AT liusong ultradeepsequencingdifferentiatespatternsofskinclonalmutationsassociatedwithsunexposurestatusandskincancerburden AT remenyikeva ultradeepsequencingdifferentiatespatternsofskinclonalmutationsassociatedwithsunexposurestatusandskincancerburden AT gellenemese ultradeepsequencingdifferentiatespatternsofskinclonalmutationsassociatedwithsunexposurestatusandskincancerburden AT colegiooscarr ultradeepsequencingdifferentiatespatternsofskinclonalmutationsassociatedwithsunexposurestatusandskincancerburden AT baxmichael ultradeepsequencingdifferentiatespatternsofskinclonalmutationsassociatedwithsunexposurestatusandskincancerburden AT xujinhui ultradeepsequencingdifferentiatespatternsofskinclonalmutationsassociatedwithsunexposurestatusandskincancerburden AT linhaifan ultradeepsequencingdifferentiatespatternsofskinclonalmutationsassociatedwithsunexposurestatusandskincancerburden AT husswendyj ultradeepsequencingdifferentiatespatternsofskinclonalmutationsassociatedwithsunexposurestatusandskincancerburden AT fosterbarbaraa ultradeepsequencingdifferentiatespatternsofskinclonalmutationsassociatedwithsunexposurestatusandskincancerburden AT paraghgyorgy ultradeepsequencingdifferentiatespatternsofskinclonalmutationsassociatedwithsunexposurestatusandskincancerburden |