子宫内膜癌组织中FHIT基因启动子区域CpG岛甲基化状况的研究

目的 :检测子宫内膜癌组织中FHIT基因启动子区域CpG岛的甲基化状况 ,分析其与临床病理特征之间的关系 ,探讨FHIT基因启动子区域CpG岛的甲基化在子宫内膜癌发生发展中的作用。方法 :采用甲基化特异的PCR方法对亚硫酸氢盐修饰过的 35例子宫内膜癌组织、癌旁组织及患者自身外周血白细胞DNA和 2 0例非癌患者子宫内膜组织DNA的FHIT基因启动子区域CpG岛的甲基化状况进行分析。结果 :癌组织中FHIT基因启动子区域CpG岛的甲基化率为 2 5 .71 % ,癌旁组织和外周血中也存在相似的甲基化率。非癌患者的子宫内膜组织中FHIT基因的CpG岛无甲基化。癌组织与非癌患者子宫内膜组织的甲基化率之间的差异有统计学意义 (P <0 .0 5 )。DNA甲基化与临床病理特征之间无相关性。FHIT基因启动子区域CpG岛的甲基化为子宫内膜癌发生中的早期事件。结论 :子宫内膜癌组织中存在FHIT基因启动子区域CpG岛的甲基化 ,CpG岛的甲基化与临床病理特征之间无相关性。DNA甲基化为子宫内膜癌发生中的早期事件。癌旁组织和外周血可用于癌相关基因启动子区域CpG岛甲基化的检测

Hypermethylation of the 5' CpG island of FHIT gene in endometrial carcinoma

Objective: To investigate the methylation status of FHIT gene in endometrial carcinoma(EC) tissues, to analysis the relationship between clinicopathological characteristics and epigenetic changes and explore the carcinogenic molecular mechanism of EC.Methods:Bisulfate-converted DNAs from 35 primary endometrial carcinoma and corresponding noncancerous endometrial tissues or case-matched peripheral blood leukocyte were analyzed for methylation of the CpG island in the promoter region of FHIT gene by methylation-specific PCR.Results: Rate of hypermethylation of FHIT gene in primary tumor series was 25.71%. No association between methylation status and clinicopathological characteristics was demonstrated. Unexpectedly, corresponding noncancerous endometrial tissues and peripheral blood leukocyte of patients showed frequently hypermethylation of FHIT gene, but no hypermethylation occoured in normal endometrial tissues. A statistically significant was found for the hypermethylation frequency of FHIT gene between tumor tissues and normal tissues from nonmalignant patients(P<0.05).Conclusions Hypermethylation of CpG island in the promoter region of FHIT gene is a early and common alterration. No correlation between hypermethylation and clinicopathological features was observed. Hypermethylated CpG island of the peripheral blood leukocyte from patients could be used as molecular markers for the early dectetion of EC.