Proapoptotic gene BAX is frequently mutated in hereditary nonpolyposis colorectal cancers but not in adenomas
Proapoptotic gene BAX is frequently mutated in hereditary nonpolyposis colorectal cancers but not in adenomas
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DOI：
10.1016/s0016-5085(98)70477-9
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发表时间：
1998-02-01
期刊：
影响因子：
29.4
通讯作者：
Yuasa, Y
中科院分区：
文献类型：
--
作者：
Yagi, OK;Akiyama, Y;Yuasa, Y
目的：p53和BAX基因与细胞凋亡有关，p53在具有微卫星突变表型的结直肠癌中不常被发现突变，但在这些癌中经常发现BAX内八个鸟嘌呤序列的移码突变。为了了解这些基因在遗传性非息肉病性结直肠癌（HNPCC）肿瘤发生中的作用，我们检测了HNPCC患者的腺瘤和癌标本中是否存在BAX突变，并确定了p53突变的频率。研究方法：13例结直肠腺瘤和24例腺癌患者HNPCC显示微卫星不稳定表型进行了筛选聚合酶链反应，变性聚丙烯酰胺凝胶电泳和直接测序。结果如下：13例腺瘤中的2例（15.4%）和24例腺癌中的13例（54.2%）显示突变模式，并通过直接测序证实在BAX重复位点有移码突变。对于p53，24例腺癌中只有1例（4.2%）显示错义突变。结论：在HNPCC结直肠癌中，BAX比腺瘤中的突变显著（P = 0.024）。p53在这些癌中不常被发现突变。这些数据表明，BAX的突变，而不是p53的突变，可能有助于腺瘤-癌的转变在HNPCC肿瘤发生。
Background ge Aims: The p53 and BAX genes have been linked to apoptosis, p53 was not frequently found to be mutated in colorectal carcinomas with a microsatellite mutator phenotype, but frame-shift mutations in a tract of eight guanines within BAX were frequently found in these carcinomas. To understand the roles of these genes in hereditary nonpolyposis colorectal cancer (HNPCC) tumorigenesis, we examined whether BAX mutations occur in adenoma and carcinoma specimens from patients with HNPCC and also determined the frequencies of p53 mutations. Methods: Thirteen colorectal adenomas and 24 adenocarcinomas from patients with HNPCC showing a microsatellite instability phenotype were screened by polymerase chain reaction followed by denaturing polyacrylamide gel electrophoresis and direct sequencing. Results: Two of the 13 adenomas (15.4%) and 13 of the 24 adenocarcinomas (54.2%) showed mutation patterns and were confirmed to have frame-shift mutations at the BAX repeat site by direct sequencing. For p53, only 1 of the 24 adenocarcinomas (4.2%) showed a missense mutation. Conclusions: In HNPCC colorectal carcinomas, BAX was significantly (P = 0.024) more mutated than in adenomas. p53 was not frequently found to be mutated in these carcinomas. These data suggest that mutations in BAX, rather than mutations in p53, may contribute to the adenoma-carcinoma transition in HNPCC tumorigenesis.