Tamura G, Sakata K, Maesawa C, Suzuki Y, Terashima M, Satoh K, Sekiyama S, Suzuki A, Eda Y, Satodate R
Department of Pathology, School of Medicine, Iwate Medical University, Morioka, Japan.
Cancer Res. 1995 May 1;55(9):1933-6.
In order to elucidate the significance of the adenoma-carcinoma sequence in gastric carcinogenesis from a genetic point of view, we examined microsatellite alterations (replication error and loss of heterozygosity) on chromosomes 2p (D2S123), 3p (D3S1317), 5q (D5S409), 9p (IFNA), and 13q (D13S153) as well as p53 gene mutations in 13 adenomas and 23 differentiated adenocarcinomas including 8 early carcinomas of the stomach. Replication error was detected in only one of the adenomas (8%, 1/13) at the D5S409 locus and in none at the other loci, and loss of heterozygosity was also an infrequent event found in one adenoma (14%, 1/7 informative cases) at D5S409 and in none at the other loci. A p53 gene mutation was detected in one (8%, 1/13) of the adenomas. Thus, microsatellite alterations and p53 gene mutations are rare events in adenomas. In differentiated adenocarcinomas, replication error was detected in 4 (17%, 4/23) at single or multiple loci, and loss of heterozygosity was observed frequently at D3S1317 (25%, 3/12), D5S409 (67%, 6/9), and IFNA (26%, 5/19). Mutations in the p53 gene were detected in 9 (39%, 9/23) of the differentiated adenocarcinomas. Microsatellite alterations on several chromosomes and mutations in the p53 gene were frequent in differentiated adenocarcinomas, even those at an early stage. These results suggest that the adenoma-carcinoma sequence is relatively rare in gastric carcinogenesis, and that the majority of differentiated adenocarcinomas of the stomach may develop through a de novo pathway.
为了从遗传学角度阐明腺瘤 - 癌序列在胃癌发生中的意义，我们检测了13例腺瘤和23例分化型腺癌（包括8例早期胃癌）中2号染色体（D2S123）、3号染色体（D3S1317）、5号染色体（D5S409）、9号染色体（IFNA）和13号染色体（D13S153）上的微卫星改变（复制错误和杂合性缺失）以及p53基因突变情况。仅在1例腺瘤（8%，1/13）的D5S409位点检测到复制错误，其他位点均未检测到；杂合性缺失在D5S409位点的1例腺瘤中也为罕见事件（14%，1/7例信息充分的病例），其他位点均未发现。在1例腺瘤（8%，1/13）中检测到p53基因突变。因此，微卫星改变和p53基因突变在腺瘤中是罕见事件。在分化型腺癌中，在单个或多个位点检测到4例（17%，4/23）复制错误，在D3S1317（25%，3/12）、D5S409（67%，6/9）和IFNA（26%，5/19）位点频繁观察到杂合性缺失。在9例（39%，9/23）分化型腺癌中检测到p53基因突变。即使是早期的分化型腺癌，多条染色体上的微卫星改变和p53基因突变也很常见。这些结果表明，腺瘤 - 癌序列在胃癌发生中相对少见，胃的大多数分化型腺癌可能通过从头途径发生。
