Abstract: Objective This project is to explore the influence of microsatellite instability (MSI), loss of heterozygosity (LOH), as well as promoter region methylation in bone morphogenetic protein 3 (BMP3) on gastric carcinoma development. Methods LOH and MSI of locus D4S2922 and D4S2964 in 50 primary gastric carcinoma specimens were detected by polymerase chain reaction\|single strand conformation polymorphism analysis (PCR\|SSCP) and methylation-specific PCR analysis in the study. Results The positive rates of MSI, LOH was 16.00% and 20.00% in 50 specimens respectively, and the frequency of LOH in lymph node metastasis cases was significantly higher than those without. TNM stage III and IV also exhibited higher LOH frequency compared with stage I and II. The positive rate of methylation on BMP3 gene promoter was 64.44% in 45 specimens. Moreover, the MSI negative group exhibited higher methylation frequency than that of MSI positive group. Conclusion These data suggested that BMP3 genetic instability and promoter methylation were initiated during the gastric carcinogenesis. LOH was detected mostly in the late stage of the gastric carcinoma progression, which indicated higher carcinoma infiltration and poor prognosis. Promotor region methylation of BMP3 gene might be causative in the gastric carcinoma cases in Chinese.

Key words: Bone morphogenetic protein 3, Gastric cancer, Microsatellite instability, Loss of heterozygosity, Methylation, PCR-SSCP, Human