Yagi O K, Akiyama Y, Nomizu T, Iwama T, Endo M, Yuasa Y
Department of First Surgery, Tokyo Medical and Dental University School of Medicine, Japan.
Gastroenterology. 1998 Feb;114(2):268-74. doi: 10.1016/s0016-5085(98)70477-9.
BACKGROUND & 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.
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.
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.
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.
p53和BAX基因与细胞凋亡有关。在具有微卫星突变体表型的结直肠癌中，p53基因很少发生突变，但在这些癌中经常发现BAX基因一段含8个鸟嘌呤的区域发生移码突变。为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患者腺瘤和癌组织标本中是否存在BAX突变，并确定了p53突变的频率。
对13例表现为微卫星不稳定表型的HNPCC患者的结直肠腺瘤和24例腺癌进行聚合酶链反应筛查，随后进行变性聚丙烯酰胺凝胶电泳和直接测序。
13例腺瘤中有2例（15.4%）和24例腺癌中有13例（54.2%）呈现突变模式，经直接测序证实BAX重复位点存在移码突变。对于p53基因，24例腺癌中只有1例（4.2%）出现错义突变。
在HNPCC结直肠癌中，BAX基因的突变显著（P = 0.024）多于腺瘤。在这些癌中，p53基因很少发生突变。这些数据表明，在HNPCC肿瘤发生过程中，BAX基因的突变而非p53基因的突变可能促成了腺瘤-癌的转变。
