P53 GENE-MUTATIONS AND PROTEIN ACCUMULATION IN HUMAN OVARIAN-CANCER
P53 GENE-MUTATIONS AND PROTEIN ACCUMULATION IN HUMAN OVARIAN-CANCER
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DOI：
10.1073/pnas.90.11.4961
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发表时间：
1993-06-01
影响因子：
11.1
通讯作者：
YANDELL, DW
中科院分区：
文献类型：
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作者：
KUPRYJANCZYK, J;THOR, AD;YANDELL, DW
染色体17 p上的p53基因突变是许多癌症恶性进展中常见的遗传变化。我们分析了38例恶性肿瘤的卵巢或腹膜苗勒管类型的证据，p53变异在DNA或蛋白质水平。遗传学研究基于单链构象多态性分析和p53基因外显子2至11的DNA测序;在79%的肿瘤中检测到突变。这些数据显示C.G对突变与雌激素治疗史之间存在统计学显著相关性。20例正常组织可以研究的患者中有2例携带p53的生殖系突变。使用单克隆抗体PAb 180 1进行p53蛋白的免疫组织化学分析。96%的错义突变与p53蛋白的异常积累有关，但无义突变、剪接突变和大多数缺失并不导致p53蛋白的积累。在低分化III期浆液性癌中p53蛋白积累与诊断时原发肿瘤大小之间存在统计学显著相关性，这可能表明p53蛋白积累加速了原发肿瘤的转移扩散。总的来说，我们的研究结果表明，p53的改变在卵巢癌中起着重要作用，包括一些患者的疾病易感性，并提出了导致这种癌症的体细胞突变的可能机制。
Mutations of the p53 gene on chromosome 17p are a common genetic change in the malignant progression of many cancers. We have analyzed 38 malignant tumors of ovarian or peritoneal mullerian type for evidence of p53 variations at either the DNA or protein levels. Genetic studies were based on single-strand conformation polymorphism analysis and DNA sequencing of exons 2 through 11 of the p53 gene; mutations were detected in 79% of the tumors. These data show a statistically significant association between mutations at C.G pairs and a history of estrogen therapy. Two of 20 patients whose normal tissue could be studied carried germ-line mutations of p53. Immunohistochemical analysis of the p53 protein was carried out using monoclonal antibody PAb180l. Ninety-six percent of the missense mutations were associated with abnormal accumulation of p53 protein, but nonsense mutations, a splicing mutation, and most deletions did not result in p53 protein accumulation. A statistically significant association between p53 protein accumulation in poorly differentiated stage III serous carcinomas and small primary tumor size at diagnosis was found, perhaps suggesting that p53 protein accumulation accelerates the metastatic spread from a primary tumor. Overall, our findings indicate that alterations of p53 play a major role in ovarian cancer, including predisposition to the disease in some patients, and suggest a possible mechanism for somatic mutations leading to this cancer.