p53 mutation in squamous cell carcinomas from psoriasis patients treated with psoralen + UVA (PUVA).
p53 mutation in squamous cell carcinomas from psoriasis patients treated with psoralen + UVA (PUVA).
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DOI：
10.1111/1523-1747.ep12319764
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发表时间：
1997-08
期刊：
影响因子：
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通讯作者：
A. Nataraj;P. Wolf;L. Cerroni;H. Ananthaswamy
中科院分区：
文献类型：
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作者：
A. Nataraj;P. Wolf;L. Cerroni;H. Ananthaswamy
患有牛皮癣的个体用补骨脂素和UVA辐射的组合治疗，通常被称为“PUVA”疗法。流行病学研究表明，PUVA治疗是牛皮癣患者患皮肤癌的危险因素。虽然PUVA治疗在实验动物中诱发皮肤癌，但目前尚不清楚PUVA治疗的牛皮癣患者中皮肤癌发病率的增加是由于PUVA的致癌作用还是由于其他因素，如UVB。由于UV和PUVA诱导不同类型的DNA损伤导致独特类型的p53突变，我们研究了PUVA治疗的银屑病患者的皮肤癌是否存在PUVA型或UV型p53突变。对来自奥地利puva治疗的17例鳞状细胞癌（SCCs）的分析显示，11例鳞状细胞癌中共有25个p53突变。大多数p53突变发生在5tpg位点。虽然先前的研究表明5tpa位点是PUVA诱变的主要靶点，但5tpg位点的替换也很常见。有趣的是，检测到的相当一部分p53突变是C- >T或CC- >TT转变，这是紫外线诱导突变的特征。由于一些银屑病患者在PUVA治疗前已经大量暴露于UVB，并且由于PUVA治疗中使用的光源在UVB区域含有小但重要的波长，因此在PUVA治疗患者的SCCs中检测到的C- >T和CC- >TT转换可能是由UVB诱导的。尽管如此，我们的研究结果表明，在接受PUVA治疗的奥地利牛皮癣患者中，PUVA和UVB都可能在皮肤癌的发展中发挥作用。
Individuals suffering from psoriasis are treated with a combination of psoralen and UVA radiation, commonly referred to as "PUVA" therapy. Epidemiologic studies have shown that PUVA therapy is a risk factor for skin cancer in psoriasis patients. Although PUVA treatment induces skin cancer in laboratory animals, it is unknown whether the increased incidence of skin cancer reported in PUVA-treated psoriasis patients is due to the carcinogenic effects of PUVA or due to other factors such as UVB. Because UV and PUVA induce different types of DNA damage resulting in unique types of p53 mutation, we investigated whether skin cancers from PUVA-treated psoriasis patients have PUVA-type or UV-type p53 mutations. Analysis of 17 squamous cell carcinomas (SCCs) from Austrian PUVA-treated patients revealed a total of 25 p53 mutations in 11 SCCs. A majority of p53 mutations occurred at 5'TpG sites. Although previous studies have shown that 5'TpA sites are the primary targets for PUVA mutagenesis, substitutions at 5'TpG sites are also quite common. Interestingly, a sizable portion of p53 mutations detected were C-->T or CC-->TT transitions, characteristic of UV-induced mutations. Because some psoriasis patients had substantial exposure to UVB before PUVA therapy and because the light sources used in PUVA therapy contained small but significant wavelengths in the UVB region, it is possible that the C-->T and CC-->TT transitions detected in SCCs from PUVA-treated patients were induced by UVB. Nonetheless, our results indicate that both PUVA and UVB may play a role in the development of skin cancer in Austrian psoriasis patients who undergo PUVA therapy.