Nakatsuru S, Yanagisawa A, Furukawa Y, Ichii S, Kato Y, Nakamura Y, Horii A
Department of Biochemistry, Cancer Institute, Tokyo, Japan.
Hum Mol Genet. 1993 Sep;2(9):1463-5. doi: 10.1093/hmg/2.9.1463.
The adenomatous polyposis coli (APC) gene, responsible for familial adenomatous polyposis, is also associated with development of sporadic tumors in digestive system as colon, stomach, or pancreas. In order to investigate whether or not APC mutations occur as an early genetic event during gastric carcinogenesis, we examined somatic mutations of APC in flat adenomas of the stomach. DNAs isolated from flat adenomas were examined by means of an RNase protection analysis coupled with polymerase chain reaction (PCR) followed by DNA sequencing of the PCR products. By screening a mutation cluster region (MCR: codons between 1286 and 1513) of APC in which two-thirds of somatic mutations were detected in colorectal tumors, somatic mutations were found in four of ten flat adenomas: three of which caused truncation of the gene product due to a nonsense mutation or 4-bp deletion; one other was a point mutation that altered amino acid from alanine to threonine. Our results imply that APC plays a crucial role in an early step of gastric carcinogenesis, as was observed in colorectal carcinogenesis.
腺瘤性息肉病 coli（APC）基因，负责家族性腺瘤性息肉病，也与消化系统散发性肿瘤如结肠癌、胃癌或胰腺癌的发生有关。为了研究 APC 突变是否作为胃癌发生过程中的早期遗传事件出现，我们检测了胃扁平腺瘤中 APC 的体细胞突变。从胃扁平腺瘤中分离的 DNA 通过核糖核酸酶保护分析与聚合酶链反应（PCR）相结合的方法进行检测，随后对 PCR 产物进行 DNA 测序。通过筛选 APC 的突变簇区域（MCR：密码子 1286 至 1513 之间），在该区域三分之二的体细胞突变在结直肠癌肿瘤中被检测到，在十个胃扁平腺瘤中有四个发现了体细胞突变：其中三个由于无义突变或 4 碱基缺失导致基因产物截短；另一个是点突变，将氨基酸从丙氨酸改变为苏氨酸。我们的结果表明，APC 在胃癌发生的早期阶段起着关键作用，正如在结直肠癌发生中所观察到的那样。
