胶质母细胞瘤14号染色体杂合性丢失的初步研究

目的 寻找胶质母细胞瘤（glioblastoma,GBM)14号染色体上可能存在肿瘤抑制基因的杂合性丢失（loss of heterozygosity,LOH)aqfa,为发现和定位肿瘤抑制基因提供线索和依据。方法 应用聚合酶链反应方法，采用荧光标记引物和377型DNA序列自动分析仪，分析了20例GBM患者14号染色体上14个微卫星多态性标记的LOH。结果 在50％（10／20）GBM患者的14号染色体上观察到LOH，在38．2％（81／212）可提供信息位点存在LOH。14p和14q的LOH率分别为32％（6／19）、50％（10／20）。在位于14q31-32．3的D14S65位点、14q21-24.1的D14S63－D14S74位点间区域检测到了较高LOH率，分别为57．1％、46．7％－47．1％。在所测位点均未检测到微卫星不稳定（microsatellite instability,MI)。结论 染色体14q上等位基因的丢失可能在GBM分子水平发病机理中起着重要作用，14q31-32.3的D14S65位点、14q21-24.1的D14S63－D14S74位点间区域可能存在与GBM相关的肿瘤抑制基因。

A preliminary study of loss of heterozygosity on chromosome 14 in glioblastoma

Objective In order to locate the deletion areas probably harboring tumor suppressor genes on chromosome 14 and provide clues for discovering novel t umor suppressor genes. Methods Fourteen loci on chromosome 14 were examined t o detect loss of heterozygosity(LOH) in 20 cases of glioblastoma(GBM) by PC R based microsatellite polymorphism analyses, in which fluorescence-labeled pri m ers and Perkin Elmer 377 DNA Sequencer were applied. Results 50% inform ative cases of GBM displayed LOH on chromosome 14; 38.2% of informative loci s howed LOH in our series, in which the most frequent LOH was observed at locus D1 4S65(57.1%) on 14q31-32.3 and in the chromosomal region from locus D14S63 (46.7 %) to D14S74(47.1%) on 14q21-24.1. 32% of informative cases displayed LOH on 1 4p and 50% on 14q. No microsatellite instability was observed. Conclusio n Loss of genetic material on chromosome 14q may play an important role in molecular gene tic pathogenesis of GBM. The chromosomal regions at D14S65 on 14q31-32.3 and f r om D14S63 to D14S74 on 14q21-24.1 may harbor novel tumor suppressor genes assoc iated with GBM.