Fujimoto K, Yamada Y, Okajima E, Kakizoe T, Sasaki H, Sugimura T, Terada M
Genetics Division, National Cancer Center Research Institute, Tokyo, Japan.
Cancer Res. 1992 Mar 15;52(6):1393-8.
Structural alterations of the p53 gene were investigated to elucidate the molecular biological difference between superficial and invasive bladder cancer by polymerase chain reaction single-strand conformation polymorphism analysis. In 25 bladder cancers obtained from 23 patients, p53 gene mutations were investigated in exon regions 4 to 11. Twenty-four were transitional cell carcinomas, and the remaining one was a squamous cell carcinoma. Only one of 13 superficial bladder cancers, including pTis, pTa, and pT1, was found to have p53 gene mutation. However, of 12 invasive bladder cancers with pT2, pT3, and pT4, six primary carcinomas, including a squamous cell carcinoma and one metastatic carcinoma, were found to have p53 gene mutations. The number of cancers examined in Grades 1, 2, and 3 was three, seven, and 15, respectively. p53 gene mutation was not found in any of the ten cancers with Grades 1 and 2, while eight of 15 bladder cancers with Grade 3 were found to have p53 gene mutation. The results indicated that the incidence of p53 gene mutations appeared to be much higher in invasive-type and high-grade bladder cancers than in superficial and low-grade ones. Our results are compatible with the recently published results by Sidransky et al. [Science (Washington DC), 252: 706-709, 1991] showing that p53 gene mutations were frequently found in invasive bladder cancers by sequence analysis on polymerase chain reaction amplified products corresponding to exons 5 to 9. Our results are also compatible with previously reported results by Olumi et al. (Cancer Res., 50: 7081-7083, 1990) showing that the loss of chromosome 17p, revealed by analysis with restriction fragment length polymorphism, was frequent in high-grade bladder cancers. In this study, p53 gene mutations were often found in exon 4 as well as in other exons. Therefore, this region should also be examined for screening of mutations of this gene in bladder cancer. There appeared to be no consistent mutation sites in exons 4 to 11 of the p53 gene and no specific patterns of the mutation in bladder cancer.
通过聚合酶链反应单链构象多态性分析，研究p53基因的结构改变，以阐明浅表性和浸润性膀胱癌之间的分子生物学差异。在从23例患者获得的25例膀胱癌中，对第4至11外显子区域进行了p53基因突变研究。其中24例为移行细胞癌，其余1例为鳞状细胞癌。在13例浅表性膀胱癌（包括pTis、pTa和pT1）中，仅1例发现有p53基因突变。然而，在12例pT2、pT3和pT4浸润性膀胱癌中，6例原发性癌（包括1例鳞状细胞癌和1例转移癌）发现有p53基因突变。1级、2级和3级检查的癌例数分别为3例、7例和15例。在10例1级和2级癌中均未发现p53基因突变，而在15例3级膀胱癌中，8例发现有p53基因突变。结果表明，p53基因突变的发生率在浸润型和高级别膀胱癌中似乎比浅表性和低级别膀胱癌高得多。我们的结果与Sidransky等人最近发表的结果[《科学》（华盛顿特区），252: 706 - 709，1991]一致，该结果表明通过对与第5至9外显子对应的聚合酶链反应扩增产物进行序列分析，在浸润性膀胱癌中经常发现p53基因突变。我们的结果也与Olumi等人先前报道的结果（《癌症研究》，50: 7081 - 7083，1990）一致，该结果表明通过限制性片段长度多态性分析发现，17号染色体短臂缺失在高级别膀胱癌中很常见。在本研究中，p53基因突变不仅经常出现在其他外显子中，也经常出现在第4外显子中。因此，在膀胱癌中筛查该基因突变时也应检查该区域。在p53基因的第4至11外显子中似乎没有一致的突变位点，在膀胱癌中也没有特定的突变模式。
