|Budget Amount *help
¥2,400,000 (Direct Cost : ¥2,400,000)
Fiscal Year 1992 : ¥500,000 (Direct Cost : ¥500,000)
Fiscal Year 1991 : ¥800,000 (Direct Cost : ¥800,000)
Fiscal Year 1990 : ¥1,100,000 (Direct Cost : ¥1,100,000)
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.