胶质母细胞瘤染色体13q上肿瘤抑制基因存在的可能性

Possibility of Existence of Tumor Suppressor Genes on Chromosome 13q in Glioblastoma

目的 寻找胶质母细胞瘤 (glioblastoma ,GBM ) 13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和 377型DNA序列自动分析仪 ,分析了 2 0例GBM 13号染色体上 14个微卫星多态性标记的LOH。结果 在 6 0 %GBM的 13号染色体上观察到LOH ,在 45 .8%可提供信息位点存在LOH。其中 13q的LOH率明显高于 13p ,13q和 13p的LOH率分别为 6 0 %、2 7%。在 13q上的下列位点上检测到较高的LOH率(>5 0 % ) :13q14.1 14.3上D13S15 3,13q12 14.2上的D13S2 17 D13S2 6 3 ,13q2 1.2 32上的D13S15 6 D13S2 6 5。结论 13号染色体可能在GBM的分子发病机制中发挥着重要作用 ,在 13q14.1 14.3上的D13S15 3位点、13q12 14.2上的D13S2 17 D13S2 6 3和 13q2 1.2 32上的D13S15 6 D13S2 6 5间区域可能存在多个与GBM相关的肿瘤抑制基因 。

Purpose: 14 loci on chromosome 13 were examined to detect loss of heterozygosity (LOH) in 20 cases of glioblastoma (GBM) in order to locate the deletion areas probably harboring tumor suppressor genes (TSGs). Methods: Polymerase chain reaction (PCR) based microsatellite polymorphism analyses were performed to detect LOH on chromosome 13, fluorescence- labeled primers and Perkin Elmer 377 DNA Sequencer were applied. Results: 60% informative cases of GBM displayed LOH on chromosme 13.60% of informative cases displayed LOH on 13q and 27% on 13p. 45.8% of informative loci showed LOH in our series, in which the higher frequent LOH were observed in the chromosomal regions from loci D13S217 to D13S263 on 13q12-14.2 and from D13S156 to D13S265 on 13q21.2-32 and at loci D13S153 on 13q14.114.3 Conclusions: Loss of genetic material on chromosome 13 may play an important role on the molecular pathogenesis of GBM. The chromosomal regions from loci D13S217 to D13S263 on 13q12-14.2 and from D13S156 to D13S265 on 13q21.2-32 and at loci D13S153 on 13q14.1-14.3 may harbor several TSGs associated with GBM, which may include novel TSGs apart from RB1.