鼻咽癌组织中GNAT1基因的表达、杂合性丢失及甲基化分析  

Expression,Loss of Heterozygosity,and Methylation of GNAT1 Gene in Nasopharyngeal Carcinoma

作　　者：易红梅[1,2] 任彩萍[1] 彭丹[1] 周亮[1] 李辉[1] 姚开泰[1] 

机构地区：[1]中南大学湘雅医学院肿瘤研究所 [2]湖南省人民医院临床医学研究所,湖南长沙410005

出　　处：《癌症》2007年第1期9-14,共6页Chinese Journal of Cancer

摘　　要：背景与目的:在鼻咽癌中,染色体3p21.3为高频缺失区,杂合性丢失(lossofheterozygosity,LOH)分析和功能学研究都表明3p21.3区存在与鼻咽癌相关的抑瘤基因。GNAT1基因也定位于3p21.3,但在鼻咽癌中未见关于GNAT1基因的研究报道。本研究旨在探讨GNAT1基因在鼻咽癌组织中的表达、LOH及甲基化情况。方法:应用逆转录-聚合酶链式反应(reversetranscriptionpolymerasechainreaction,RT-PCR)方法检测了33例鼻咽癌组织和15例慢性鼻咽炎组织中GNAT1基因的表达,并通过微卫星分析技术和甲基化特异性聚合酶链式反应(methylation-specificpolymerasechainreaction,MSP)分析GNAT1基因LOH和启动子区甲基化情况。结果:GNAT1基因在慢性鼻咽炎组织中均稳定表达,而在72.7%(24/33)的鼻咽癌组织中表达下调或缺失,显著低于慢性鼻咽炎组织(100%,15/15)(P=0.022);LOH分析显示鼻咽癌组织中GNAT1基因的杂合性丢失率为15%(3/20),且LOH与基因表达存在相关性(P=0.016);甲基化分析发现在100%的鼻咽癌组织和80%慢性鼻咽炎组织中存在GNAT1基因启动子区高甲基化。结论:GNAT1基因在鼻咽癌组织中表达下调或缺失,这一现象与GNAT1基因的LOH存在相关性,而与3p21.3区基因启动子区CpG岛的甲基化可能无关。GNAT1基因的甲基化可能不是鼻咽癌的发病机制。BACKGROUND ＆ OBJECTIVE： In nasopharyngeal carcinoma （NPC）, chromosome 3p21.3 is a high frequency deletion region. Evidences from both loss of heterozygosity （LOH） and functional studies showed that there may exists NPC-related tumor suppressor genes on 3p21.3. This study was to investigate the expression, LOH, and methylation of GNAT1 gene, which locates at 3p21.3, in NPC. METHODS： The expression of GNAT1 in 33 specimens of primary NPC and 15 specimens of chronic nasopharyngitis tissue was detected by reverse transcription-polymerase chain reaction （RT-PCR）. LOH and promoter methylation status of GNAT1 were examined by microsatellites analysis and methylation- specific polymerase chain reaction （MSP）. RESULTS： GNAT1 was expressed stably in all chronic nasopharyngitis tissues, while absent or down-regulated in 24 （72.7%） specimens of NPC （P=0.022）. LOH analysis showed allele loss of GNAT1 in 3 （15%） specimens of NPC. LOH of GNAT1 was correlated to its expression level （P=0.016）. Methylation analysis showed hypermethylation of GNAT1 promoter in all primary NPC tissues and in 12 （80%） specimens of chronic nasopharyngitis tissues. CONCLUSIONS： Expression of GNAT1 gene is down-regulated or absent in NPC tissues, which may relate to allele loss of GNAT1 in NPC, but not relate to its promoter hypermethylation. Hypermethylation of GNAT1 may not be oncogenic mechanisms of NPC.

关 键 词：鼻咽肿瘤 抑瘤基因 GNAT1基因 杂合性丢失 甲基化 

分 类 号：R739.6[医药卫生—肿瘤]