Aoki T, Takeda S, Yanagisawa A, Kato Y, Ajioka Y, Watanabe H, Kudo S, Nakamura Y
Department of Biochemistry, Cancer Institute, Tokyo, Japan.
Hum Mutat. 1994;3(4):342-6. doi: 10.1002/humu.1380030403.
To investigate genetic features in small and flat colorectal carcinomas that arise de novo, we searched for genetic alterations in six sporadic tumors by examining their APC, K-ras, and p53 genes. Two of the six tumors carried detectable mutations within the mutation cluster region (MCR) of the APC gene; both mutations were predicted to cause truncation of the gene product. Four tumors carried mutations of the p53 gene; three were missense mutations in exon 5, and the other was a 3-bp deletion in exon 6. However, neither codon 12 nor codon 13 of K-ras contained detectable mutation in any tumors. Hence, as "adenoma-carcinoma sequence" model of development of colorectal carcinoma, inactivation of the APC and p53 genes appear to be involved in development of the de novo type of colorectal carcinoma even though the adenoma stage is not observed.
为了研究原发性发生的小而扁平的结直肠癌的基因特征，我们通过检测六个散发性肿瘤的APC、K-ras和p53基因来寻找基因改变。六个肿瘤中有两个在APC基因的突变簇区域（MCR）内携带可检测到的突变；两个突变均预计会导致基因产物截短。四个肿瘤携带p53基因突变；三个是外显子5的错义突变，另一个是外显子6的3个碱基缺失。然而，在任何肿瘤中K-ras的第12密码子和第13密码子均未检测到突变。因此，作为结直肠癌发生的“腺瘤-癌序列”模型，即使未观察到腺瘤阶段，APC和p53基因的失活似乎也参与了原发性结直肠癌的发生。
