A ROLE FOR SUNLIGHT IN SKIN-CANCER - UV-INDUCED P53 MUTATIONS IN SQUAMOUS-CELL CARCINOMA
A ROLE FOR SUNLIGHT IN SKIN-CANCER - UV-INDUCED P53 MUTATIONS IN SQUAMOUS-CELL CARCINOMA
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DOI：
10.1073/pnas.88.22.10124
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发表时间：
1991-11-01
影响因子：
11.1
通讯作者：
PONTEN, J
中科院分区：
文献类型：
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作者：
BRASH, DE;RUDOLPH, JA;PONTEN, J
阳光是一种致癌物质，每个人都会接触到。其紫外线成分是皮肤鳞状细胞癌的主要流行病学危险因素。肿瘤进展的多个步骤。如果那些与阳光相关的基因含有针对紫外线的突变，那么它们就会被揭示出来。在一系列新英格兰和瑞典患者中，我们发现 14/24 (58%) 的皮肤浸润性鳞状细胞癌含有 p53 肿瘤抑制基因突变，每种突变都改变了氨基酸序列。三个肿瘤中存在 CC --> TT 双碱基变化表明紫外线参与了这些 p53 突变，目前已知这种变化仅由紫外线诱导。 UV 还与仅在二嘧啶位点发生类似 UV 的突变有关，包括高频率的 C --> T 取代。内部恶性肿瘤中的 p53 突变不显示这些 UV 特异性突变。二嘧啶特异性还暗示含有胞嘧啶的二嘧啶光产物是致癌光产物。我们相信这些结果确定了参与随后人类癌症的基因中与致癌物相关的步骤。
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.