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目的 探讨胶质母细胞瘤 (glioblastoma,GBM)发病的分子遗传学机理 ,确定 GBM的发生发展主要和哪些染色体或染色体区域有关 ,哪些染色体区域上可能存在与 GBM相关的肿瘤抑制基因 (tu-mor suppressor gene,TSG)。方法 应用聚合酶链反应技术 ,采用荧光标记的引物和 377型 DNA序列自动分析仪 ,对 2 1例 GBM的所有 2 2对常染色体上共计 382个微卫星位点进行了杂合性丢失 (loss of het-erozygosity,L OH)分析 ,相邻 2个微卫星位点之间的平均遗传学距离为 10 c M。结果 在所有被检测的染色体臂上都观察到 L OH,其中以染色体 10 q、10 p、9p、17p和 13q的 L OH率最高 (>5 0 % ) ,这些染色体臂上已知的肿瘤抑制基因 PTEN、DMBT1、p16、p15、p5 3和 Rb所在区域 L OH率都较高 ;14q、3q、2 2 q、11p、9q、19q上也存在较高的 L OH率 (>40 .5 % ) ;首次发现多个共同微小丢失区域 :9p2 2 - 2 3、10 p12 .2 - 14、10 q2 1.3、13q12 .1- 14.1、13q14.3- 31、17p11.2 - 12、17p13、3q2 4- 2 7、11p12 - 13、14q31- 32 .3、14q2 1- 2 4.1、2 2 q13.2 - 13.3、4q35、4q31.1- 31.2、6 qtel、6 q16 .3。结论 GBM存在复杂的遗传学异常 ,涉及多条染色体臂。以 10 q、10 p、9p、17p和 13q的异常与 GBM发生发展的关系最为密切?
Objective To investigate the molecular genetic mechanism of glioblastoma (GBM) and determine which chromosomes or chromosome regions are responsible for the occurrence and development of GBM. Which chromosomal regions may have tuMOR-related tumor suppressor genes suppressor gene, TSG). Methods A total of 382 microsatellite loci on 2 2 pairs of autosomes of 2 1 GBM were detected by polymerase chain reaction (PCR) and fluorescence-labeled primers and 377 automatic DNA sequence analyzer of het-erozygosity, LOH), the average genetic distance between two microsatellite loci was 10 cM. Results LOH was observed on all detected chromosomal arms, with the highest LOH rates (> 50%) on chromosomes 10q, 10p, 9p, 17p and 13q, the known tumor suppression on these chromosomal arms The LOH rates of the regions PTEN, DMBT1, p16, p15, p5 3 and Rb were high, and the higher L OH ratio (> 40.5%) existed in 14q, 3q, 2 2q, 11p, 9q and 19q, ); For the first time, a number of common small lost regions were found: 9p2 2 - 2 3,10 p12 .2 - 14,10 q2 1.3,13 q12 .1 - 14.1,13 q14.3 - 31,17p11.2 - 12,17p13,3q2 4 - 2 7, 11p12 - 13, 14q31 - 32 .3, 14q2 1- 2 4.1, 22 q13.2 - 13.3, 4q35, 4q31.1 - 31.2,6 qtel, 6 q16 .3. Conclusion GBM has complex genetic abnormalities involving multiple chromosome arms. Abnormalities of 10 q, 10 p, 9 p, 17 p and 13 q are most closely related to the occurrence and development of GBM?