胶质母细胞瘤6号染色体杂合性丢失的初步研究

目的：寻找胶质母细胞瘤（GBM）6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，采用荧光标记的引物及377型DNA序列自动分析仪，分析了21例GBM患者6号染色体上20个微卫星多态性标记的LOH。结果：6号染色体总的LOH检出率为47．6％（10／21），在28．1％（81／288）能提价信息位上检测了LOH。其中，6p和6q的LOH检出率分别是28．6％（6／21）、38．1％（8／21），在6q^tel上距短臂端粒201．1cM的微卫星位点D6S281检测到较高的LOH率（50％），6q^16.3上D6S287的LOH率也高达50％，另外，6p^21.1-21.3上D6S276的LOH率也较高（35．3％）。结论：6号染色体分子遗传学异常改变可能在GBM的发生发展中起着重要作用，染色体6q^tel上的D6S281位点,6q^16.3上的D6S287和6p^21.1-21.3的D62S276位点所在的染色体区域可能存在与GBM相关的肿瘤抑制基因。

Loss of heterozygosity on chromosome 6 in glioblastoma

Purpose:20 loci on chromosome 6 were examined to detect loss of heterozygosity(LOH)in 21 cases of glioblastoma(GBM) in order to locate the deletion areas probably harboring tumor suppressor genes.Methods:PCR based microsatellite polymorphism analyses were performed to detect LOH on chromosome 6, fluorescence labeled primers and Perkin Elmer 377 DNA Sequencer were applied.Results:47.6% informative cases of GBM displayed LOH on chromosome 6, 28.1% of informative loci showed LOH in our series, in which the most frequent LOH were observed at locus D6S281 (50%) on 6q tel and D6S287(50%) on 6q 16.3 ,the LOH frequency at locus D6S276 on 6p 21.1 21.3 is also high(35.3%).Conclusions:Loss of genetic material on chromosome 6 may be involved in the molecular genetic pathogenesis of GBM. The chromosomal regions at loci D6S281 on 6q tel ,D6S287 on 6q 16.3 and D6S276 on 6p 21.1 21.3 may harbor tumor suppressor genes associated with GBM. [