Pattern of p53 gene mutations in breast cancers of women of the midwestern United States.
Pattern of p53 gene mutations in breast cancers of women of the midwestern United States.
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DOI：
10.1093/jnci/84.4.246
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发表时间：
1992-02
期刊：
影响因子：
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通讯作者：
S. Sommer;J. Cunningham;R. McGovern;S. Saitoh;J. Schroeder;L. Wold;J. Kovach
中科院分区：
文献类型：
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作者：
S. Sommer;J. Cunningham;R. McGovern;S. Saitoh;J. Schroeder;L. Wold;J. Kovach
背景p53基因突变是人类癌症中最常见的遗传性病变。p53基因的突变模式在不同的癌症中不同，可能是一个有用的流行病学工具，用于识别致癌因素。我们的目的是确定居住在美国中西部地区的妇女乳腺癌中p53突变的模式是否与美国和欧洲其他地区乳腺癌患者以及其他上皮性肿瘤中p53突变的模式相似。方法利用我们最近开发的用于分析实体瘤触摸标本中肿瘤细胞簇基因组DNA中p53突变的技术，我们对44例乳腺癌中该基因的外显子5-9和相邻剪接点进行了测序。来自每个肿瘤的细胞也用识别p53蛋白的不同表位的三种单克隆抗体染色。结果44例乳腺癌中14例（32.6%）检测到p53基因突变。只有一半的突变是错义突变。另一半包括五个微缺失（三个产生移码），一个单碱基取代产生终止密码子，一个单碱基取代产生剪接点异常。在44例癌症中，8例存在p53抗原的核表达，其中6例p53基因存在半合子错义突变。结论：我们的乳腺癌人群中p53突变的模式不同于其他研究者在乳腺癌人群中报道的大多数p53突变是错义的。在我们人群中的14个突变中，至少有5个显著改变了p53的结构，这表明p53基因失活的隐性机制可能比其他人群更常见。中西部妇女乳腺癌和其他人群乳腺癌中p53突变模式的差异可能反映了选择偏倚或目前可用的小样本量。然而，我们的数据是兼容的可能性，一个内源性或外源性因素影响p53在某些妇女与乳腺癌在中西部在更大程度上比在美国和欧洲的其他地区。
BACKGROUND Mutation in the p53 gene is the most common genetic lesion in human cancers. The pattern of mutation in the p53 gene differs among cancers and may be a useful epidemiological tool for identification of factors contributing to carcinogenesis. PURPOSE Our purpose was to determine if the pattern of p53 mutation in breast carcinomas in our population of women residing in the midwestern region of the United States is similar to the pattern of p53 mutation in breast cancers in patients from other regions of the United States and Europe and in other epithelial tumors. METHODS With a technique we recently developed for the analysis of p53 mutations in genomic DNA from tumor cell clusters in touch preparations of solid tumors, we sequenced exons 5-9 and adjacent splice junctions of the gene in 44 breast cancers. Cells from each tumor were also stained with three monoclonal antibodies which recognize different epitopes of the p53 protein. RESULTS We detected p53 mutations in 14 (32.6%) of 44 breast carcinomas. Only half of the mutations were missense changes. The other half included five microdeletions (three producing frame-shifts), one single-base substitution generating a stop codon, and one single-base substitution generating a splice junction abnormality. Nuclear expression of p53 antigen was present in eight of 44 cancers, including six with hemizygous missense mutations in the p53 gene. CONCLUSIONS The pattern of p53 mutations in our breast cancer population differs from that reported in breast cancer populations by other investigators in which most p53 mutations were missense. Among 14 mutations in our population, at least five drastically altered the structure of p53, suggesting that a recessive mechanism of inactivation of the p53 gene may be more common than in other populations. IMPLICATIONS Differences in the pattern of p53 mutation in breast cancers in Midwestern women and in breast cancers in other populations may reflect selection bias or small sample sizes currently available. However, our data are compatible with the possibility that an endogenous or exogenous factor influences p53 carcinogenesis in some women with breast cancer in the Midwest to a greater extent than in other regions of the United States and Europe.