非小细胞肺癌11个肿瘤相关基因启动子CpG岛甲基化的研究  

Promoter hypermethylation of 11 tumor-related genes in non-small cell lung cancers

作　　者：杨振华[1] 蔡映云[2] 孙丽华[1] 于坚[3] 朱景德[3] 

机构地区：[1]江苏省南京市第一医院呼吸科,2100061 [2]复旦大学附属中山医院肺科 [3]上海市肿瘤研究所

出　　处：《临床内科杂志》2005年第10期708-710,共3页Journal of Clinical Internal Medicine

基　　金：国家863高科技研究发展项目(2002AA2Z3352);上海市自然科学基金项目(02DJ14056)

摘　　要：目的观测11个基因在非小细胞肺癌中的甲基化谱,探讨肺癌基因诊断的新途径。方法应用甲基化特异性的PCR(m ethyl-spec ific PCR,MSP)。方法检测甲基化率,回收产物测序。结果11个基因中有6个基因在癌组织中的甲基化率均>40%并且高于癌旁组织,6个基因的甲基化率分别是APC 61%,RASSF1 a 55%,p73 45%,p16 INK4 a 43%,CDH13 43%及RAR-β41%,>65岁组RASSF1 a、p16 INK4 a和RAR-β甲基化率高于≤65岁组;吸烟史组APC、RASSF1 a、p16 INK4 a和CDH13的甲基化率高于无吸烟史组;腺癌组APC、CDH13和RAR-β甲基化率高于鳞癌组,而鳞癌组p16 INK4 a甲基化率高于腺癌组;RASSF1 a和p16 INK4 a甲基率随TNM临床分期而逐渐增加。结论6个基因甲基化率的发生具有肿瘤特异性,并且相关基因的甲基化与NSCLC患者的病理生理密切相关,我们的研究为早期诊断NSCLC提供帮助。Objective To explore the clinieopathologieal significance of gene promoter methylation in non-small cell lung oancer（NSCLC）. Methods MSP was employed to determine the methylation status. PCR product was sequenced using pGEM-T vector. Results The frequencies of methylation for six genes were：61% for APC,55% for RASSFla,45% for p73,43% for p16INK4a,43% for CDH13 and 41% for RAR-β Methylation of RASSFla ,pl6INK4a and RAR-13 was more frequent in 〉 65 group. Methylation of APC ,RASSFla,pl6INK4a and CDH13 was more frequent in smoking group. Methylation of APC,CDH13 and RAR-β was more frequent in AdC group,while p16INK4a was frequent in SCC group. Methylation of RASSFla and p16INK4a was much more frequent in advanced TNM stage. Conclusion Methylation of six genes correlated with age ,smoking,histological and TNM stage. Our research enable us to develop the novel diagnostic and prognostic tools of NSCLC.

关 键 词：非小细胞肺癌 肿瘤相关基因 启动子CpG岛 甲基化 

分 类 号：R734.2[医药卫生—肿瘤]