Aim: To investigate the relation between gastric cancer and microsatellite instability (MSI), loss of heterozygosity (LOH) and promoter region methylation.
Methods: Fifty primary gastric carcinoma specimens were collected from patients with no family history of cancer. In addition, normal tissues were also collected from patients as controls. DNA was extracted by polymerase chain reaction for single-strand conformation polymorphism, bisulfite DNA sequencing, and methylation-specific band analysis.
Results: The positive rate for MSI and LOH in gastric carcinoma was 16% and 20%, respectively. According to the tumor, node and metastasis staging system, the LOH frequency was higher in gastric carcinoma at stages III and IV than in gastric carcinoma at stages I and II (P = 0.01), which was also significantly correlated with lymph node metastasis and clinico- pathological characteristics of gastric carcinoma. Methylation of bone morphogenetic protein 3 (BMP3) gene promoter was detected in 64.44% of gastric carcinoma tissue samples. However, no statistical significance was observed between promoter region methylation and carcinoma differentiation. Interestingly, the BMP3 gene methylation rate was 71.05% and 28.58%, respectively, in MSI positive and negative cases (P = 0.031), suggesting that BMP3 genetic instability and promoter methylation are initiated during gastric carcinogenesis. LOH was detected mostly in the late stages of gastric carcinoma, indicating that gastric carcinoma at late stages has a higher infiltration and a poorer prognosis.
Conclusion: Promotor region methylation of the BMP3 gene may cause gastric carcinoma in Chinese people.
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