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

Douglas E. Brash, Jeffrey A. Rudolph, Jeffrey A. Simon, Anthony Lin, Gregory J. Mckenna, Howard P. Baden, Alan J. Halperin, Jan Pontén

Research output: Contribution to journalArticle

1556 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)10124-10128
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume88
Issue number22
DOIs
StatePublished - Jan 1 1991

Keywords

  • Tumor suppressor genes
  • UV light

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