FHIT基因甲基化检测对肺癌早期诊断的临床意义

目的探讨人原发性肺癌中FHIT基因启动子区的甲基化状态及其临床意义。方法采用甲基化特异性聚合酶链技术（MSP），对59例人原发性肺癌组织（肺癌组）、32例肺正常组织（正常组）、15例癌旁组织（癌旁组）及11例支气管鳞状化生组织进行FHIT基因5’-CpG岛甲基化状况检测，甲基化阳性标本采用基因克隆测序技术进行序列测定。结果肺癌组、癌旁组和正常组的FHIT基因甲基化率分别为37．3％（22／59）、20．0％（3／15）、0（0／32），三组相比差异有统计学意义（P〈0．01）；支气管鳞状化生组织的甲基化阳性率为18．1％（2／11）。FHIT基因甲基化率肺癌吸烟者与非吸烟者差异无统计学意义（P〉0．05）。FHIT甲基化扩增产物测序结果显示，所有CpG岛中的胞嘧啶均保持不变，而CpG岛二核苷酸以外的胞嘧啶经过PCR扩增后，则被胸腺嘧啶取代。结论FHIT基因5’-CpG岛甲基化参与了肺癌的演变，可能在肺癌发生的早期阶段，采用MsP方法进行FHIT甲基化检测，可能对肺癌的早期诊断具有一定的临床意义。

Detection of Promoter Hypermethylation of FHIT Gene in Lung Cancer and its Clinical Significance

Objective To illustrate the relationship between the methylation of FHIT promoter with the development of lung cancer. Methods 59 lung cancer samples, 32 normal lung, 15 adjacent non-carcinoma tissues and 11 bronchial squamous epithelium were used for analysing the methylation of FHIT genes. The FHIT positive samples were sequenced by clone method and DNA sequencer. Results FHIT methylation of lung cancer tissue samples, adjacent non-carcinoma tissue samples and surrounding normal lung tissue samples were 37.3% （22/59） ,20.0% （3/15）and 0 （0/32）respectivly, showing a significant difference （ P 〈 0.01 ） ; Methylation was found in 2 （ 18.1% ） of 11 bronchial squamous epithelial samples. No significant difference of FHIT methylation rate between the smoker and nonsmoker （ P 〉 0.05 ）. Conclusion The incidence of 5＇- CpG island methylation of FHIT is an early event of lung cancer. Analysis of Methylation status of FHIT promoter might be helpful to the early diagnosis of lung cancer.