Cell biological study on the alterations of oncogenes and suppressor genes in human gastric adenoma and carcinoma

本研究旨在分析各种癌基因和抑癌基因在人胃腺癌和胃癌中的变化和表达. RAS、MYC、FOS和ERBB 2基因在胃腺瘤中均未检测到扩增。然而，基因产物表达量为100%。其中，p185<ERBB2>在43例（65%）胃腺瘤、19例（33%）早期胃癌和45例（44%）晚期胃癌中检测到。67例胃腺瘤中无p53阳性表达，4例腺瘤中癌中有2例阳性表达，9例早期胃癌中有3例阳性表达，96例进展期胃癌中有36例阳性表达。10例胃腺瘤中有3例p53点突变，6例高分化腺癌（WDA）中有4例p53点突变，10例低分化腺癌（PDA）中有5例p53点突变。p53突变是胃癌发生发展早期的常见事件.在19例有信息的病例中，13例检出17 p的洛缺失。WDAs在早期癌症中5 q（60%）和17 p（67%）的洛频率较高，在晚期癌症中1 q（67%）、5 q（36%）、7 p（33%）、7 q（39%）和17 p（73%）的LOH频率较高。在PDAs中，洛在1 p（38%）、12 q（31%）和17 p（60%）处检测到，但在1 q、5 q和7 p处未检测到。ERBB 2、k-SAM和c-MET基因仅在进展期胃癌中扩增。ERBB 2基因在WDA中的扩增率为18%，而k-SAM基因在PDA中的扩增率为33%。而c-MET基因在WDA中的扩增率为13.5%（5例），在PDAs中的扩增率为26%（10例），提示在胃腺瘤和胃癌的发生、增殖和发展过程中存在着多基因的聚集。胃WDA和PDA之间存在共同的和不同类型的基因改变。

This study was conducted to analyze the alterations and expressions of various oncogenes and suppressor genes in human gastricadenom and carcinoma.1. No amplification of RAS, MYC, FOS and ERBB2 genes was detected in gastric adenomas. However, the gene products expressed variably. Of these, p185^<ERBB2> was detected in 43(65%) gastric adenomas, 19(33%) early cancers, and 45(44%) advanced cancers.2. p53 immunoreactivity was found in none of 67 gastric adenomas, 2of 4 carcinoma in adenomas, 3 of 9 early cancers and 36 of 96 advanced cancers, respectively. p53 point mutations were demonstarated in 3 of10 gastric adenomas, 4 of 6 well differentiated adenocarcinomas (WDA), and 5 of 10 poorly differentiated adenocarcinmas (PDA). p53 mutation is a common event in gastric carcinoma occurring from the early stage of progression.3. LOH of 17p was detected in 13 of 19 informative cases. WDAs showed high frequencies of LOH on 5q(60%) and 17p(67%) in early cancers, and 1q(67%), 5q(36%), 7p(33%), 7q(39%), and 17p (73%) in advanced cancers. In PDAs, LOH was detected on 1p(38%), 12q(31%), and 17p(60%), but not on 1q, 5q, adn 7p.4. ERBB2, k-SAM, and c-MET genes amplified only in advanced gastriccarcinomas. Frequency of amplification was 18% for ERBB2 gene only inWDAs and 33% for k-SAM gene only in PDAs. On the other hand, c-MET gene ampfilication was 13.5%(5 cases)in WDAs and 26%(10 cases)in PDAs.These results overall suggest that multiple gene alterations were accumulated in the tumorigenesis, proliferation and progression of human gastric adenoma and carcinoma. Moreover, there exist common and differint types of gene alterations between gastric WDAs and PDAs.