Department of Oncology, First People's Hospital of Taizhou, No. 218 Hengjie Road, Huangyan District, Taizhou 318020, Zhejiang Province, China.
World J Gastroenterol. 2010 Mar 21;16(11):1409-13. doi: 10.3748/wjg.v16.i11.1409.
To investigate the relation between gastric cancer and microsatellite instability (MSI), loss of heterozygosity (LOH) and promoter region methylation.
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.
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.
Promotor region methylation of the BMP3 gene may cause gastric carcinoma in Chinese people.
探讨胃癌与微卫星不稳定性（MSI）、杂合性缺失（LOH）和启动子区甲基化的关系。
收集 50 例无癌症家族史的原发性胃癌患者的肿瘤组织标本，同时收集患者的正常组织作为对照。采用聚合酶链反应单链构象多态性、亚硫酸氢盐 DNA 测序和甲基化特异性带分析方法提取 DNA。
胃癌的 MSI 和 LOH 阳性率分别为 16%和 20%。根据肿瘤、淋巴结和转移分期系统，III 期和 IV 期胃癌的 LOH 频率高于 I 期和 II 期胃癌（P=0.01），且与淋巴结转移和胃癌的临床病理特征密切相关。检测到 64.44%的胃癌组织样本中骨形态发生蛋白 3（BMP3）基因启动子发生甲基化。然而，启动子区甲基化与癌组织分化之间无统计学意义。有趣的是，MSI 阳性和阴性病例的 BMP3 基因甲基化率分别为 71.05%和 28.58%（P=0.031），提示 BMP3 遗传不稳定性和启动子甲基化是胃癌发生的早期事件。LOH 主要发生在胃癌晚期，表明晚期胃癌浸润程度更高，预后更差。
中国人的胃癌可能与 BMP3 基因启动子区甲基化有关。
