THE SEQUENTIAL ACCUMULATION OF GENETIC ALTERATIONS CHARACTERISTIC OF THE COLORECTAL ADENOMA-CARCINOMA SEQUENCE DOES NOT OCCUR BETWEEN GASTRIC ADENOMA AND ADENOCARCINOMA
THE SEQUENTIAL ACCUMULATION OF GENETIC ALTERATIONS CHARACTERISTIC OF THE COLORECTAL ADENOMA-CARCINOMA SEQUENCE DOES NOT OCCUR BETWEEN GASTRIC ADENOMA AND ADENOCARCINOMA
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DOI：
10.1002/path.1711760307
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发表时间：
1995-07-01
影响因子：
7.3
通讯作者：
SATODATE, R
中科院分区：
文献类型：
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作者：
MAESAWA, C;TAMURA, G;SATODATE, R
我们筛选了30个胃腺瘤和72个胃腺癌的4个基因改变（K-ras、APC和p53基因突变和DCC基因位点杂合性丢失），这些基因改变是已知的发生在结直肠肿瘤发生过程中的。我们使用聚合酶链反应（PCR）单链构象多态性分析来检测突变。DCC基因座的杂合性缺失（洛）通过对基因内可变数目的串联重复序列进行PCR直接确定。K-ras基因突变在任何胃腺瘤或胃癌中均未检测到。APC突变在20%（6/30）的腺瘤中检测到，但仅在1.4%（1/72）的癌中检测到。相比之下，p53基因在癌中频繁突变（35%; 25/72），但在腺瘤中没有。DCC基因座的洛缺失在癌中常见（58%; 11/19例有信息的病例），但在腺瘤中不常见（14%; 1/7）。p53和DCC基因的改变在分化型和未分化型胃癌中均有发生。胃腺瘤与胃癌之间的遗传变异发生率差异很大，提示在胃癌发生过程中，从腺瘤到胃癌的顺序性发展并不常见。
We screened 30 gastric adenomas and 72 gastric adenocarcinomas for four genetic alterations (mutations of the K-ras, APC, and p53 genes and loss of heterozygosity at the DCC genetic locus) which are known to occur during colorectal tumourigenesis. We used polymerase chain reaction (PCR) single-strand conformation polymorphism analysis to detect mutations. Loss of heterozygosity (LOH) at the DCC locus was ascertained directly by performing PCR on the variable number of tandem repeats within the gene. Mutations of the K-ras gene were not detected in any gastric adenoma or carcinoma. APC mutations were detected in 20 per cent (6/30) of the adenomas but in only 1.4 per cent (1/72) of the carcinomas. In contrast, the p53 gene was frequently mutated in carcinomas (35 per cent; 25/72), but not in adenomas. LOH at the DCC locus was a frequent occurrence in carcinomas (58 per cent; 11/19 informative cases) but was infrequent in adenomas (14 per cent; 1/7). Alterations of the p53 and DCC genes occurred frequently both in differentiated and in undifferentiated gastric carcinomas. The considerable differences in the incidences of genetic alterations between gastric adenoma and carcinoma indicate that the sequential development of gastric carcinoma from adenoma is uncommon in gastric carcinogenesis.