甲状腺乳头状癌中TSHR基因启动子区5’-CpG岛甲基化研究  

Studies on methylation of 5'-CpG island in the promoter region of TSHR gene in papillary thyroid carcinomas

作　　者：许敬[1,2] 葛明华[3] 凌志强[4] 程蕾[4,5] 徐加杰[3] 

机构地区：[1]温州医学院附属第一医院肿瘤外科,温州325035 [2]浙江省舟山医院肿瘤科,舟山316000 [3]浙江省肿瘤医院头颈肿瘤外科,杭州310022 [4]浙江省肿瘤医院肿瘤研究所分子病理研究室,杭州310022 [5]浙江中医药大学第一临床医学院肿瘤内科,杭州310053

出　　处：《肿瘤》2010年第8期696-699,共4页Tumor

基　　金：浙江省医药卫生科学研究基金计划(编号:2010KYA037);浙江省卫生高层次创新人才培养工程基金[编号:浙卫发(2008)134号]

摘　　要：目的:探讨促甲状腺素受体(thyroid-stimulating hormone receptor,TSHR)基因启动子区5'-CpG岛甲基化在甲状腺乳头状癌发生发展中的作用,加深对其癌变分子机制的了解。方法:应用实时荧光定量甲基化特异性聚合酶链反应(real-timefluorescent quantitative methylation-specific PCR,qMSP)分别检测90例甲状腺乳头状癌患者癌组织及癌旁正常组织中TSHR基因启动子区5'-CpG岛甲基化情况,并分析其与临床病理参数之间的关系。结果:在90例甲状腺乳头状癌组织中,TSHR基因启动子区5'-CpG岛发生甲基化的有37例(41.1%,37/90),与之相对应的癌旁正常组织中发生甲基化的有5例(5.6%,5/90),2者差异有统计学意义(P<0.05)。TSHR基因启动子区5'-CpG岛甲基化分别与患者的肿瘤大小、病灶多少、局部侵犯、淋巴结转移及临床分期有关(P<0.05),而与患者的性别、年龄等无关(P>0.05)。结论:TSHR基因启动子区5'-CpG岛的甲基化是甲状腺乳头状癌频发的分子事件,这可能是导致甲状腺细胞摄碘率下降的重要原因之一,在甲状腺乳头状癌的发生发展过程中发挥着重要作用。Objective ：To investigate the role of the 5＇ -CpG island methylation in the promoter region of thyroid-stimulating hor- mone receptor （TSHR） gene in the carcinogenesis and progression of papillary thyroid carcinomas （PTC） , and elucidate the molecular mechanism underlying PTC carcinogenesis. Methods：The 5＇ -CpG island methylation in the promoter region of TSHR gene was detected using real-time fluorescent quantitative methylation-speeific PCR （qMSP） in tumor tissues and corresponding adjacent thyroid tissues isolated from 90 patients with PTC. The relationship between the methyaltion status of TSHR 5＇ -CpG island and clinical pathological parameters was analyzed. Results： Methylation of TSHR promoter 5 ＇ -CpG island was detected in 37 specimens out of 90 cases of tumor tissues （37/90, 41.1% ） and only in 5 specimens out of 90 cases of corresponding adjacent thyroid tissues （5/90, 5.6% ）. The rate of methylation of TSHR promoter in PTC was higher than that in adjacent thyroid tissures （P 〈 0.05 ）. The 5 ＇ -CpG island methylation of TSHR gene promoter correlated with tumor size, number of lesions, local invasion, lymph node metastasis, and clinical stage, respectively （ P 〈 0.05 ）, but not with gender and age of patients （ P 〉 0.05 ）. Conclusion ： Methylation of 5＇ -CpG island in the promoter region of TSHR gene is a molecular event that frequently occurred in the tumorigenesis of PTC, which may be an important reason for the decreased iodide-uptake by thyroid cells. Methylation of 5 ＇ -CpG island in the promoter region of TSHR gene played an important role in the carcinogenesis and development of PTC.

关 键 词：甲状腺肿瘤 癌 乳头状 受体 促甲状腺素 DNA甲基化 实时荧光定量甲基化聚合酶链反应 

分 类 号：R736.1[医药卫生—肿瘤]