Dams E, Van de Kelft E J, Martin J J, Verlooy J, Willems P J
Department of Medical Genetics, University of Antwerp, UIA, Belgium.
Cancer Res. 1995 Apr 1;55(7):1547-9.
We have analyzed DNA obtained from 10 glioblastomas multiforme and 6 astrocytomas for microsatellite instability, using 17 different microsatellite loci dispersed over 7 different chromosomes. Six of 16 gliomas showed 1 or more microsatellite alterations in tumor DNA as compared to constitutional DNA. We observed microsatellite instability resulting in allelic shifts in 5 of 10 glioblastomas multiforme but not in any of the astrocytomas. Loss of an allele was observed in 3 glioblastomas multiforme. An imbalance in the intensity of alleles was noticed in 1 astrocytoma and in 1 glioblastoma multiforme. In 1 glioblastoma multiforme, an extra allele was present at two distinct loci. Overall, 5.3% of microsatellite analyses showed an abnormality. We conclude that microsatellite instability is present at a low grade in glioblastomas multiforme but to a lesser extent in astrocytomas. Genomic instability in human gliomas, therefore, should not be regarded as a mechanism for tumor initiation but as an evolution in tumor progression.
我们使用分布在7条不同染色体上的17个不同微卫星位点,分析了取自10例多形性胶质母细胞瘤和6例星形细胞瘤的DNA的微卫星不稳定性。与正常DNA相比,16例胶质瘤中有6例在肿瘤DNA中显示出1个或更多微卫星改变。我们观察到10例多形性胶质母细胞瘤中有5例出现微卫星不稳定性导致的等位基因移位,而星形细胞瘤中均未出现。在3例多形性胶质母细胞瘤中观察到一个等位基因缺失。在1例星形细胞瘤和1例多形性胶质母细胞瘤中发现等位基因强度失衡。在1例多形性胶质母细胞瘤中,两个不同位点存在额外等位基因。总体而言,5.3%的微卫星分析显示异常。我们得出结论,多形性胶质母细胞瘤中存在低水平的微卫星不稳定性,但在星形细胞瘤中程度较轻。因此,人类胶质瘤中的基因组不稳定性不应被视为肿瘤起始机制,而应被视为肿瘤进展过程中的一种演变。