胶质母细胞瘤9号染色体肿瘤抑制基因的研究

目的寻找胶质母细胞瘤(GBM)9号染色体上可能存在肿瘤抑制基因的杂合性丢失(LOH)区域,为发现和定位肿瘤抑制基因(TSG)提供线索和依据.方法应用聚合酶链反应(PCR)方法,采用荧光标记引物和377型DNA序列自动分析仪,分析2l例GBM9号染色体上20个微卫星多态性标记的LOH.结果21例GBM中,在14例的9号染色体上检测到LOH,33.0%(93/282)可提供信息位点存在LOH.在9p和9q上存在LoH的GBM分别有14例和10例.在位于9p21-23的D9S286位点以及9p21的D9S285～D9S157位点间区域检测到较高LOH率,分别为52.6%、43.8%～46.7%.结论染色体9p上等位基因的丢失可能在GBM分子水平发病机制中起着重要作用.在9p21-23的D9S286位点、9p21的D9S285～D9S157位点间区域可能存在与GBM相关的多个TSG,可能包括位于9p21上的p16和p15基因,在p16、p15所在染色体区域的远端9p21-23可能存在其他未知的TSG.

A study of tumor suppressor genes on chromosome 9 in glioblastomas.

Objective To locate the deletion regions possibly harboring tumor suppressor genes on chromosome 9 with a view to facilitating the identification of novel tumor suppressor genes in glioblastoma(GMB) .Methods 20 loci on chromosome 9 were examined to detect loss of heterozygosity(LOH) in 21 cases of glioblastoma by PCR based microsatellite polymorphism analy-ses, in which fluorescence-labeled primers and Perkin Elmer 377 DNA Sequencer were applied. Results 66.7%(14/21) infor-mative cases of GBM displayed LOH on chromosome 9, 33.0%(93/282) of informative loci showed LOH in our series, in which the most frequent LOH was observed at locus D9S286(52. 6% ) on 9p21-23 and in the chromosomal region from locus D9S285(43.8%) to D9S157(46.7%) on 9p21. 66.7% of informative cases displayed LOH on 9p and 47.6% on 9q. Conclusions Loss of genetic material on chromosome 9p may play an important role in the molecular genetic pathogenesis of GBM. The chromo-somal regions at D9S286 on 9p21-23 and from D9S285 to D9S157 on 9p21 may harbor several tumor suppressor genes associated with GBM. Besides the well-known TSGs p16 and p15, a novel TSG may be present on the region distal to p16 and p15.