Somatic mutations in facial skin from countries of contrasting skin cancer risk.

Autor: King C; Wellcome Sanger Institute, Hinxton, UK., Fowler JC; Wellcome Sanger Institute, Hinxton, UK., Abnizova I; Wellcome Sanger Institute, Hinxton, UK., Sood RK; Wellcome Sanger Institute, Hinxton, UK., Hall MWJ; Wellcome Sanger Institute, Hinxton, UK.; Department of Oncology, University of Cambridge, Hutchinson Research Centre, Cambridge Biomedical Campus, Cambridge, UK., Szeverényi I; Skin Research Institute of Singapore and Institute of Medical Biology, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.; Institute of Aquaculture and Environmental Safety, Georgikon Campus, Hungarian University of Agricultural and Life Sciences, Keszthely, Hungary., Tham M; Skin Research Institute of Singapore and Institute of Medical Biology, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore., Huang J; Skin Research Institute of Singapore and Institute of Medical Biology, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore., Young SM; Department of Ophthalmology, National University Hospital, Singapore, Singapore., Hall BA; Department of Medical Physics and Biomedical Engineering, University College London, London, UK., Birgitte Lane E; Skin Research Institute of Singapore and Institute of Medical Biology, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore., Jones PH; Wellcome Sanger Institute, Hinxton, UK. pj3@sanger.ac.uk.; Department of Oncology, University of Cambridge, Hutchinson Research Centre, Cambridge Biomedical Campus, Cambridge, UK. pj3@sanger.ac.uk.
Jazyk: angličtina
Zdroj: Nature genetics [Nat Genet] 2023 Sep; Vol. 55 (9), pp. 1440-1447. Date of Electronic Publication: 2023 Aug 03.
DOI: 10.1038/s41588-023-01468-x
Abstrakt: The incidence of keratinocyte cancer (basal cell and squamous cell carcinomas of the skin) is 17-fold lower in Singapore than the UK 1-3 , despite Singapore receiving 2-3 times more ultraviolet (UV) radiation 4,5 . Aging skin contains somatic mutant clones from which such cancers develop 6,7 . 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 populations 8-13 . 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.
(© 2023. The Author(s).)
Databáze: MEDLINE
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