King, Charlotte;
Fowler, Joanna C;
Abnizova, Irina;
Sood, Roshan K;
Hall, Michael WJ;
Szeverényi, Ildikó;
Tham, Muly;
... Jones, Philip H; + view all
(2023)
Somatic mutations in facial skin from countries of contrasting skin cancer risk.
Nature Genetics
10.1038/s41588-023-01468-x.
(In press).
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Abstract
The incidence of keratinocyte cancer (basal cell and squamous cell carcinomas of the skin) is 17-fold lower in Singapore than the UK1-3, despite Singapore receiving 2-3 times more ultraviolet (UV) radiation4,5. Aging skin contains somatic mutant clones from which such cancers develop6,7. We hypothesized that differences in keratinocyte cancer incidence may be reflected in the normal skin mutational landscape. Here we show that, compared to Singapore, aging facial skin from populations in the UK has a fourfold greater mutational burden, a predominant UV mutational signature, increased copy number aberrations and increased mutant TP53 selection. These features are shared by keratinocyte cancers from high-incidence and low-incidence populations8-13. In Singaporean skin, most mutations result from cell-intrinsic processes; mutant NOTCH1 and NOTCH2 are more strongly selected than in the UK. Aging skin in a high-incidence country has multiple features convergent with cancer that are not found in a low-risk country. These differences may reflect germline variation in UV-protective genes.
| Type: | Article |
|---|---|
| Title: | Somatic mutations in facial skin from countries of contrasting skin cancer risk |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/s41588-023-01468-x |
| Publisher version: | https://doi.org/10.1038/s41588-023-01468-x |
| Language: | English |
| Additional information: | © 2023 Springer Nature Limited. This article is licensed under a Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/). |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Med Phys and Biomedical Eng |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10175260 |
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