胶质瘤DMBT1基因杂合性缺失和微卫星不稳定性的研究  

LOH Analysis of DMBT1 Gene and MSI in Human Gliomas

作　　者：杨卫忠 王锐 石松生[2] 陈建屏[2] 刘才兴[2] 林于峰[2] 倪天瑞[2] 

机构地区：[1]福建省神经外科研究所 [2]福建医科大学附属协和医院神经外科,福建福州350001

出　　处：《中国神经肿瘤杂志》2004年第3期208-211,共4页Chinese Journal of Neuro-Oncology

摘　　要：背景与目的:近年来,发现杂合性缺失(Ioss of heterozygosity,LOH)和微卫星不稳定性(microsatelliteinstability,MSI)参与肿瘤的发生及发展,属于肿瘤发生的一种新机制。本文探讨胶质瘤抑癌基因的改变,可以为今后胶质瘤进行基因诊断和基因治疗提供新的探索方向。探讨 DMBTI 基因(deleted in malignant brain tumors)杂合性缺失和微卫星不稳定性在胶质瘤发生和恶性进展中的作用。方法:应用微卫星多态性分析技术检测10例正常脑组织、10例脑膜瘤、80例胶质瘤10q25.3～26.1区域内5个多态性微卫星标记(D10S187.D10S209,D10S216,D10S575,D10S587),分析 DMBT1基因 LOH 和 MSI。结果:10例良性脑膜瘤和胶质瘤旁正常脑组织均未发现 MSI 和 DMBT1基因 LOH。30例胶质瘤组织至少有1个微卫星标记发生 LOH,Ⅰ级胶质瘤为15.4%(2/13例),Ⅱ级为22.7%(5/2例),Ⅲ级为35.3%(6/17例),Ⅳ级60.7%(17/28例)。其中,Ⅳ级胶质瘤中D10S209和 D10S587发生 LOH 频率>50%,D10S187 LOH 发生率为43.5%。D10S216和 D10S575 LOH 发生率均<30%。80例胶质瘤组织共有19例 MSI,Ⅰ级胶质瘤 MSI 发生率为7.7%(1/13例).Ⅱ级为9.1%(2/22例).Ⅲ级为23.5%(4/17例),Ⅳ级42.9%(12/28例)。DMBT1基因 LOH 和 MSI 与胶质瘤病理分级明显相关(P<0.05),其中,Ⅲ～Ⅳ级胶质瘤 DMBT1基因 LOH 和 MSI 均明显高于Ⅰ～Ⅱ级(P<0.05)。结论:抑癌基因DMBT1基因 LOH 和胶质瘤 MSI 与胶质瘤发生和分化密切相关。BACKGROUND & OBJECTIVE:Recently,LOH and MSI were found to play a role in carcino- genesis and they maybe a newly identified mechanism for carcinogenesis.The researches of the anti-oncogene changes will provide new and more effective strategies of gene diagnosis and gene therapy.In this paper,gene dele- tions of deleted in malignant brain tumors(DMBTI)gene in human gliomas were investigated.METHODS:With the control of 10 normal brain samples and 10 benign meningiomas,5 microsatellite markers in 10q25.3～26.1 in 80 human gliomas were detected by PCR.RESULTS:There were 30 deletions(37.5%)of DMBTI gene and 19 MSI(23.8%)in 80 gliomas,while it was no found in 10 normal brain samples and 10 benign meningiomas.A significant correlation was observed between DMBT1 gone deletions and/or MSI and WHO grades of gliomas.CON- CLUSIONS:The DMBTI gene deletions and/or MSI contributed to glioma carcinogenesis and differentiation.

关 键 词：胶质瘤 LOH DMBT1基因 杂合性缺失 微卫星不稳定性 MSI 发生率 瘤组织 正常 脑组织 

分 类 号：R735[医药卫生—肿瘤] R739[医药卫生—临床医学]