摘要
目的 O6 甲基鸟嘌呤 DNA甲基转移酶 (O6 methylguanineDNAmethyltransferase ,MGMT)在烷化剂所致DNA损伤的修复中起重要作用 ,启动子区过甲基化而导致MGMT基因的转录失活。本文探索了喉癌中MGMT基因启动子区过甲基化状态及其mRNA表达情况。方法 采用甲基化特异性聚合酶链反应及半定量逆转录聚合酶链反应 (reversetranscriptionpolymerasechainreaction ,RT PCR)法分析喉癌、癌旁和正常喉部组织中MGMT基因启动子区过甲基化状态及其mRNA表达情况。结果 4 6例喉癌组织中有 16例 (34 8% )MGMT基因启动子过甲基化 ,相应的癌旁及正常组织中均无甲基化。MGMT基因甲基化在不同的病理分级 (χ2 =3 130 ,P =0 0 77)和临床TNM分期 (χ2 =3 95 7,P =0 138)中差异无显著性。所有甲基化的癌组织中均无MGMTmRNA表达 ,而所有非甲基化的癌组织、相应癌旁组织和 5例正常组织中均有MGMTmRNA表达。且非甲基化的癌组织中MGMTmRNA表达较癌旁组织 (t=30 5 4 0 ,P <0 0 1)和正常组织 (t=31 882 ,P <0 0 1)强 ,而癌旁和正常组织之间差异无显著性(t=0 4 19,P =0 6 77)。
Objective O6 methylguanine DNA methyltransferase (MGMT) is a DNA repair protein It plays a important role in the repair of DNA damage caused by the exposure to methylating agents Hypermethylation of CpG islands in the promoter regions result in MGMT genes loss of transcription This study explored the hypermethylation of CpG islands in the promoter regions of MGMT genes in laryngeal squamous cell carcinoma Methods Methylation specific PCR and semiquantify RT PCR were used to study the promoter methylation of the MGMT gene and loss of transcription in laryngeal carcinoma tissues, tissues adjacent to the tumor and normal laryngeal tissues Results Among the 46 laryngeal carcinoma, MGMT gene hypermethylation was present in 16 case(34 8%) MGMT hypermethylation was not detected in all tissues adjacent to the tumors and 5 normal tissues There is no statistical significant difference of promoter hypermethylation among the samples of different histological grade(χ 2=3 130, P =0 077) or samples from patients with different TNM stages(χ 2=3 957, P =0 138) No expression of MGMT mRNA was found in all hypermethylated laryngeal carcinoma tissues Expression of MGMT mRNA was detected in all unmethylated laryngeal carcinoma tissues, tissues adjacent to the tumors and 5 normal tissues Expression of MGMT mRNA in unmethylated laryngeal carcinoma tissues is higher than tissues adjacent to the tumors ( t =30 540, P <0 01) and normal tissues( t =31 882, P <0 01) There is no statistical significant difference of MGMT mRNA Expression between tissues adjacent to the tumors and normal tissues( t =0 419, P =0 677) Conclusion MGMT gene promoter hypermethylation is associated with loss of its transcription in laryngeal carcinoma tissues
出处
《中华耳鼻咽喉科杂志》
CAS
CSCD
北大核心
2004年第3期152-156,共5页
Chinese Journal of Otorhinolaryngology
基金
国家杰出青年科学基金资助项目 ( 3 992 5 0 3 5 )
高等学校博士学科点专项科研基金资助项目( 2 0 0 2 0 4870 62 )
