河南食管癌高发区居民食管癌变过程中微卫星LOH的特征  

Characterization of loss of heterozygosity (LOH) in multistage carcinogenesis of esophageal cancer (EC) at the high-incidence area for EC in Henan

作　　者：安继业[1] 高姗姗[1] 庄则豪[1] 秦艳茹[1] 范宗民[1] 王立东[1] 

机构地区：[1]郑州大学医学院癌症研究室

出　　处：《肿瘤》2005年第4期311-315,共5页Tumor

基　　金：国家杰出青年科学基金资助项目(编号:30025016)河南省高校创新人才工程基金资助项目(编号:1999125)河南省医药卫生创新人才工程基金资助项目(编号:200084)

摘　　要：目的微卫星(microsatellite)是广泛分布于生物基因组中的DNA重复序列,与许多重要基因紧密连锁。本研究旨在探讨食管癌变多阶段演进过程中微卫星DNA杂合缺失(lossofheterozygosity,LOH)的特征及其意义。方法采用微卫星DNA多态分析法,选取染色体3p、5q、6p、9p、13q、17p、17q和18q的15个多态微卫星位点,对32例食管癌前病变和癌组织进行LOH分析。结果食管各级癌前病变组织和癌组织均出现不同程度的微卫星DNALOH,其频率随病变程度加重而明显升高(除D9S1752位点外,P均<0.05);其中D9S171、D13S260和TP53位点在癌阶段,LOH频率均超过60%。各级癌前病变组织和癌组织中发生LOH的位点不尽相同,同一个体从基底细胞过度增生→间变→原位癌→鳞状细胞癌,均发生LOH的位点是:D3S1234和TP53。结论基因水平的改变发生在食管癌变的早期阶段,随病变程度加重,基因组不稳定性增强,可能是导致食管癌前病变持续向癌的方向发展的重要机制之一。Objective Microsatellites are the repeated DNA sequences distributed widely within the human genomes and closely linked with many important genes. This study was designed to characterize the changes of microsatellite DNA LOH in esophageal carcinogenesis. Methods Allelic deletions in 32 cases of matched precancerous, cancerous and normal tissues were examined by microsatellite polymorphism analysis using 15 polymorphic markers on chromosomes 3p, 5q, 6p, 9p, 13q, 17p, 17q and 18q.Results Microsatellite DNA LOH was observed in precancerous and cancerous tissues, except D9S1752. The rate of LOH increased remarkably with the lesions progressed from basal cell hyperplasia （BCH） to squamous cell carcinoma （SCC） （P〈0.05）. Three markers, D9S171, D13S260 and TP53 showed the highest incidence of LOH （〉60%）. LOH loci were different in precancerous and cancerous tissues. LOHs in both D3S1234 and TP53 were the common events in different lesions from the same patients. Conclusion Microsatellite DNA LOHs occur in early stage of human esophageal carcinogenesis, even in BCH.With the lesion progresses, gene instability increases, the accumulation of these changes may be one of important mechanisms to drive precancerous lesion to cancer.

关 键 词：食管肿瘤 癌前状态 局灶性上皮增生 DNA 卫星 杂合子丢失 

分 类 号：R735.1[医药卫生—肿瘤]