Arai M, Shimizu S, Imai Y, Nakatsuru Y, Oda H, Oohara T, Ishikawa T
Department of Pathology, Faculty of Medicine, University of Tokyo, Japan.
Int J Cancer. 1997 Feb 7;70(4):390-5. doi: 10.1002/(sici)1097-0215(19970207)70:4<390::aid-ijc3>3.0.co;2-r.
In contrast to the origins of colorectal carcinomas, the mechanisms of carcinogenesis in the small intestine remain unclear. We therefore analyzed the mutational status of the Ki-ras, p53, and adenomatous polyposis coli (APC) genes in primary carcinomas of the small intestine and compared the mutation patterns with those established for colorectal cancers. DNA was extracted from 15 formalin-fixed, paraffin-embedded lesions. Codons 12, 13 and 61 of the Ki-ras gene, exons 5-8 of the p53 gene, and codons 1268-1569, which contain the mutation cluster region (MCR) of the APC gene, were amplified by means of PCR, subcloned and sequenced. Mutations of the Ki-ras and p53 genes were observed in 8 (53.3%) and 4 lesions (26.7%), respectively. The mutational frequency of the Ki-ras gene in the present series of small intestinal carcinomas was similar, while that of the p53 gene was slightly lower than the reported frequencies for colorectal carcinomas. Only one case showed a mutation of the APC gene, involving an insertional mutation of an adenine at codons 1554-1556 with formation of a stop codon immediately downstream. Since the occurrence of an APC mutation is considered an early event in colorectal carcinogenesis, our findings indicating an extremely low frequency of such changes in and around the MCR suggest that carcinomas of the small intestine arise via a genetic pathway distinct from that involved in the development of carcinomas of the colorectum.
与结直肠癌的起源不同，小肠癌发生的机制仍不清楚。因此，我们分析了小肠原发性癌中Ki-ras、p53和腺瘤性息肉病基因（APC）的突变状态，并将突变模式与已确定的结直肠癌的突变模式进行比较。从15个福尔马林固定、石蜡包埋的病变组织中提取DNA。通过PCR扩增Ki-ras基因的第12、13和61密码子、p53基因的第5-8外显子以及包含APC基因的突变簇区域（MCR）的第1268-1569密码子，进行亚克隆并测序。分别在8个（53.3%）和4个病变组织（26.7%）中观察到Ki-ras和p53基因的突变。本系列小肠癌中Ki-ras基因的突变频率相似，而p53基因的突变频率略低于报道的结直肠癌的频率。仅1例显示APC基因发生突变，涉及第1554-1556密码子处腺嘌呤的插入突变，并在紧邻下游形成一个终止密码子。由于APC突变的发生被认为是结直肠癌发生过程中的早期事件，我们的研究结果表明MCR及其周围此类变化的频率极低，这提示小肠癌通过与结直肠癌发生不同的遗传途径产生。
