A role for sunlight in skin-cancer – UV-induced p53 mutations in squamous-cell carcinoma
Open accessAbstract
Sunlight is a carcinogen to which everyone is exposed. Its UV component is the major epidemiologic risk factor for squamous cell carcinoma of the skin. Of the multiple steps in tumor progression, those that are sunlight-related would be revealed if they contained mutations specific to UV. In a series of New England and Swedish patients, we find that 14/24 (58%) of invasive squamous cell carcinomas of the skin contain mutations in the p53 tumor suppressor gene, each altering the amino acid sequence. Involvement of UV light in these p53 mutations is indicated by the presence in three of the tumors of a CC----TT double-base change, which is only known to be induced by UV. UV is also implicated by a UV-like occurrence of mutations exclusively at dipyrimidine sites, including a high frequency of C----T substitutions. p53 mutations in internal malignancies do not show these UV-specific mutations. The dipyrimidine specificity also implicates dipyrimidine photoproducts containing cytosine as oncogenic photoproducts. We believe these results identify a carcinogen-related step in a gene involved in the subsequent human cancer.
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NER is the most versatile repair system.
“NER is the most versatile repair system and eliminates a wide repertoire of DNA lesions, among which are UV-induced CPD and 6-4PP, that represent the main determinants in solar mutagenesis and skin cancer [105,106].”
From Mind the gap: keeping UV lesions in check (2011) · cites this paper as [105]
NER removes many DNA lesions, among them UV-induced CPD and 6-4PP.
“NER is the most versatile repair system and eliminates a wide repertoire of DNA lesions, among which are UV-induced CPD and 6-4PP, that represent the main determinants in solar mutagenesis and skin cancer [105,106].”
From Mind the gap: keeping UV lesions in check (2011) · cites this paper as [105]
CPD and 6-4PP are key drivers of sunlight-induced mutagenesis and skin cancer.
“NER is the most versatile repair system and eliminates a wide repertoire of DNA lesions, among which are UV-induced CPD and 6-4PP, that represent the main determinants in solar mutagenesis and skin cancer [105,106].”
From Mind the gap: keeping UV lesions in check (2011) · cites this paper as [105]
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- Authors
- Brash, D. E., Rudolph, J. A., Simon, J. A., Lin, A., McKenna, G. J., Baden, H. P., Halperin, A. J., & Pontén, J.
- Affiliations
- Yale University (US)
- Harvard University (US)
- Uppsala University (SE)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1991-11-15
- Volume
- 88
- Issue
- 22
- Pages
- 10124-10128
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC52880
- OpenAlex
- W1967629365
- Cited by
- 1,959
- References
- 52
- Citations by year
- 2026: 20 · 2025: 20 · 2024: 37 · 2023: 33 · 2022: 39 · 2021: 46 · 2020: 58 · 2019: 43 · 2018: 56 · 2017: 48 · 2016: 70 · 2015: 51 · 2014: 63 · 2013: 52 · 2012: 50
- FWCI
- 71.48
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Cancerfonden
- National Institutes of Health (5p01ca039238-09)
- National Cancer Institute (CA39238)
- Topics
- Health Sciences › Medicine › Epidemiology › Nonmelanoma Skin Cancer Studies
- Health Sciences › Medicine › Dermatology › Skin Protection and Aging
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
- Keywords
- ultraviolet radiation, skin cancer, squamous cell carcinoma, TP53 mutation, tumor suppressor, carcinogenesis, sun exposure
- MeSH terms
- Aged, Amino Acid Sequence, Base Sequence, Carcinoma, Squamous Cell, Exons, Female, Humans, Male, Middle Aged, Molecular Sequence Data, Neoplasms, Radiation-Induced, Oligodeoxyribonucleotides, Skin Neoplasms, Sunlight, Ultraviolet Rays, Polymerase Chain Reaction, Genes, p53, Tumor Suppressor Protein p53
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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