Cited by 1,959Nonmelanoma Skin Cancer StudiesSkin Protection and AgingCarcinogens and Genotoxicity Assessment

A role for sunlight in skin-cancer – UV-induced p53 mutations in squamous-cell carcinoma

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Brash, D E, Rudolph, J A, Simon, J A, Lin, A, McKenna, G J, Baden, H P, Halperin, A J, Pontén, J·1991·Proceedings of the National Academy of Sciences

Abstract

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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Crossref · 10.1073/pnas.88.22.10124

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52 of 52 references verified0 citation errors · 0 not checkable

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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
Published
1991-11-15
Volume
88
Issue
22
Pages
10124-10128
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
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
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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