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

Journal Article · Fri Nov 15 04:00:00 EST 1991 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.88.22.10124· OSTI ID:5815730

Brash, D E; Rudolph, J A; Simon, J A; Lin, A; McKenna, G J ^[1]; Baden, H P ^[2]; Ponten, J ^[3]

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1. Yale School of Medicine, New Haven, CT (United States)
2. Dermatopathology Associates of New York, New Rochelle, NY (United States)
3. Univ. Hospital, Uppsala (Sweden)

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, the authors 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 {yields} 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 {yields} 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. They believe these results identify a carcinogen-related step in a gene involved in the subsequent human cancer.

• OSTI ID: 5815730
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (United States) Vol. 88:22; ISSN PNASA; ISSN 0027-8424
• Country of Publication: United States
• Language: English

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AMINES
AZINES
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
BODY
CARCINOGENESIS
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ORGANIC OXYGEN COMPOUNDS
ORGANS
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RADIATION EFFECTS
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RADIOINDUCTION
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SUN
THYMINE
ULTRAVIOLET RADIATION
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