Taniguchi Y, Gemma A, Takeda Y, Takenaka K, Niitani H, Kudoh S, Shimada T
Fourth Department of Internal Medicine, Nippon Medical School Main Hospital, Tokyo, Japan.
Lung Cancer. 1996 Jun;14(2-3):219-28. doi: 10.1016/0169-5002(95)00548-x.
We analyzed 29 pairs of primary and metastatic lung carcinomas obtained at autopsy for mutations in the p53 gene, using the polymerase chain reaction-single strand conformation polymorphism method (PCR-SSCP). We examined the relationship between p53 gene mutations and the development of metastasis, and the stability of p53 gene mutations during chemotherapy. The tumors consisted of six small cell carcinomas, 13 adenocarcinomas, eight squamous cell carcinomas, one large cell carcinoma, and one adeno-squamous cell carcinoma. PCR-SSCP analysis showed that three small cell carcinomas (50%), three adenocarcinomas (23%), two squamous cell carcinomas (25%), and one large cell carcinoma (100%) had p53 gene mutations. All these abnormalities were found between exon five and exon eight. The mutations in the primary tumors and the metastatic tumors were identical. These results suggest that p53 gene mutations occur before distant metastases develop, and that they may be stable during the process of metastasis. There were nine metastatic tumor samples that existed before the patients received chemotherapy. These samples showed identical p53 mutations as the corresponding primary tumor. This suggests that anticancer drugs rarely induce p53 gene mutations.
我们使用聚合酶链反应-单链构象多态性方法(PCR-SSCP)对29对在尸检时获取的原发性和转移性肺癌进行p53基因突变分析。我们研究了p53基因突变与转移发生之间的关系,以及化疗期间p53基因突变的稳定性。肿瘤包括6例小细胞癌、13例腺癌、8例鳞状细胞癌、1例大细胞癌和1例腺鳞癌。PCR-SSCP分析显示,3例小细胞癌(50%)、3例腺癌(23%)、2例鳞状细胞癌(25%)和1例大细胞癌(100%)存在p53基因突变。所有这些异常均出现在第5外显子和第8外显子之间。原发性肿瘤和转移性肿瘤中的突变相同。这些结果表明,p53基因突变发生在远处转移形成之前,并且在转移过程中可能是稳定的。有9份转移性肿瘤样本在患者接受化疗之前就已存在。这些样本显示出与相应原发性肿瘤相同的p53突变。这表明抗癌药物很少诱导p53基因突变。