108例视网膜母细胞瘤Rb基因突变的特征  

THE CHARACTERISTICS OF Rb GENE MUTATIONS IN 108 CASES OF RETINOBLASTOMA.

作　　者：黄倩[1] Thaddeus P.Dryja  David W.Yandell 

机构地区：[1]华西医科大学附属第一医院眼科 [2]美国哈佛大学医学院眼耳医院 [3]美国佛蒙特州立大学医学院病理系

出　　处：《中华眼底病杂志》1997年第1期12-16,共5页Chinese Journal of Ocular Fundus Diseases

摘　　要：目的：研究ＲＢ患者肿瘤及体细胞内Ｒｂ基因的存在状态、细微结构、Ｒｂ基因突变的特征、起源与传递。方法：ＤＮＡ分子杂交、ＳＳＣＰ分析、ＤＮＡ序列测定。结果：１０８例ＲＢ肿瘤标本中８０例（７４％）存在Ｒｂ基因点突变，其中４４例为纯合型，２０例有二个独立发生的杂合型点突变，１６例只检出一个杂合型点突变。通过对比分析ＲＢ患者肿瘤与白细胞ＤＮＡ、ＲＢ患者家庭成员白细胞ＤＮＡＲｂ基因的结构，揭示了Ｒｂ基因点突变的起源与遗传特征。结论：Ｒｂ基因是与ＲＢ肿瘤形成关系最为密切的基因。ＲＢ肿瘤发生需二次突变事件导致Ｒｂ基因的二个等位基因失活，第一次突变事件突出表现为点突变；第二次突变事件主要是ＬＯＨ。PURPOSE:To investigate the status and detailed structure of Rb gene in primary tumors and somatic cells of patients with retinoblastoma.To identify the character,origin and transmission of oncogenic point mutations.METHODS:DNA hybridization,SSCP analysis and PCR associated direct sequencing.RESULTS:Among 108 RB patients examined 80 cases were found to have subtle alterations affecting Rb locus,including 44 cases with homozygous Rb point mutations,20 cases with two independent heterozygous Rb point mutations,16 cases with heterozygous mutations involved in one allele of Rb gene.Majority of bilateral RB patients and a small fraction of unilateral RB patients were detected to have a germline mutation.In addition the higher frequency of new germline mutation and parental origin of mutation were observed.CONCLUSION:Rb gene is closely associated with retinoblastoma.Two mutation events and resulting inactivations of both Rb alleles are required for RB tumorigenesis.Based on our own data,the first event is exclusively point mutation.As for the second event,LOH accounts for two third of cases,point mutation for one third of cases.

关 键 词：视网膜母细胞瘤 RB基因 点突变 聚合酶链反应 

分 类 号：R739.72[医药卫生—肿瘤]