Yamada S, Ajioka Y, Watanabe H, Hashidate H, Takaku H, Kazama S, Yokoyama J, Nishikura K, Fujiwara T, Asakura H
First Department of Pathology, Niigata University School of Medicine, Niigata, Niigata 951-8510, Japan.
Jpn J Cancer Res. 2001 Feb;92(2):161-6. doi: 10.1111/j.1349-7006.2001.tb01078.x.
The aim of this study was to elucidate whether or not p53 genetic heterogeneity would occur while colorectal carcinoma was limited to the mucosa. Eight cases of endoscopically resected colorectal intramucosal carcinomas were analyzed to determine the p53 gene sequence (exons 5 to 8). Six out of 8 cases showed p53 gene mutations, and in all of them, the mutational status was heterogeneous. In 4 cases, mutated codons were heterogeneous as well. These data indicate that p53 gene alterations in colorectal carcinomas occur and diverge at the stage of intramucosal carcinoma, supporting our previously proposed hypothesis that colorectal carcinomas can be composed of various subclones as regards p53 gene mutation, while the carcinoma is limited to the mucosa, and one of these subclones commences invasion to the submucosa after clonal selection, thus generating a monoclonal invasive carcinoma.
本研究的目的是阐明当结直肠癌局限于黏膜层时是否会发生p53基因异质性。分析了8例经内镜切除的结直肠黏膜内癌病例，以确定p53基因序列（外显子5至8）。8例中有6例显示p53基因突变，且所有病例的突变状态均为异质性。在4例中，突变密码子也是异质性的。这些数据表明，结直肠癌中的p53基因改变在黏膜内癌阶段就已发生并出现分歧，支持了我们之前提出的假说，即就p53基因突变而言，结直肠癌在局限于黏膜层时可由各种亚克隆组成，其中一个亚克隆在克隆选择后开始侵犯黏膜下层，从而产生单克隆浸润性癌。
