复发前后多形性胶质母细胞瘤的等位基因谱分析

目的：研究多形性胶质母细胞瘤（glioblastoma multiforme,GBM)复发前后的分子遗传学变化，了解基因组范围内哪些染色体区域可能与GBM复发有关。方法：应用聚合酶链反应技术为基础的杂合性丢失（loss of heterozygosity,LOH)分析法，采用荧光标记的引物和377型DNA序列自动分析仪，检测了1例复发前后GBM所有22对常染色体上多达382个微卫星位点。相邻2个微卫星位点之间的平均距离为10cM。结果：对原发肿瘤标本的等位基因谱分析显示，染色体9p21上D9S157位点和10q21.3-26.3上D10S537、D10S185、D10S192、D10S597、D10S587、D10S217位点存在LOH。对复发肿瘤标本的研究显示，不但9p21和10q21.3-26.3上LOH的范围扩大，而且在其它多条染色体上也出现了LOH（包括1q,7p,7q,21q,20p,20q,10p,19p,19q)。结论：染色体9p和10q可能在该例GBM的发生中起着重要作用。尽管该病例复发前后的病理诊断相同，复发后GBM存在着更广泛的分子遗传学异常改变，可能伴随着更多肿瘤抑制基因的失活。

An allelotype study of primary and corresponding recurrent glioblastoma multiforme

Objective To investigate molecular genetic alterations associated with primary and corresponding recurrent glioblastoma multiforme(GBM) and to identify which chromosomal regions of the whole genome may be involved in the recurrence of primary GBM. Methods A high resolution allelotyping study of one patient's primary GBM and corresponding recurrent GBM was performed by PCR based loss of heterozygosity(LOH) analysis with the use of 382 fluorescent dye labeled polymorphic microsatellite markers covering all 22 autosomes. The mean genetic distance between two flanking markers is 10 cM. Results LOH at locus D9S157 on 9p21 and at loci D10S537, D10S185, D10S192, D10S597, D10S587, D10S217 on 10q21.3 26.3 was observed in the primary GBM. As for corresponding recurrent tumor, LOH was observed not only in expanded regions on 9p21 and 10q21.3 26.3 but also on multiple other chromosomal arms, including 1q, 7p,7q, 21q, 20p,20q,10p,19p,19q. Conclusion Chromosome 9p and 10q may be involved in the development of this GBM. Although histopathological diagnoses of the primary and corresponding recurrent tumor are identical, the recurrence of GBM is characterized by an increased involvement of molecular genetic abnormalities and may be accompanied by inactivation of more tumor suppressor genes.