von Deimling A, Albrecht S, Wiestler O D
Institut für Neuropathologie der Universität Bonn.
Verh Dtsch Ges Pathol. 1994;78:423-6.
A study was carried out to examine whether genetic loci which have been shown to exhibit loss of heterozygosity in gliomas are involved in the process of malignant progression from low grade astrocytomas to anaplastic variants. We have analyzed 18 well differentiated astrocytomas WHO grade II (A II) and 26 anaplastic astrocytomas WHO grade III (A III) for loss of heterozygosity (LOH) on chromosomes 1p, 1q, 9p, 9q, 10p, 10q, 11p, 13q, 17p, 19p, 19q and 22q and for amplification of the EGFR receptor. A PCR-based assay with microsatellite repeat sequences was employed for the detection of polymorphisms on silver-stained polyacrylamide gels. LOH on 9p was seen in 1/18 (6%) informative cases of A II and 4/25 (16%) informative cases of A III. LOH on 17p was observed in 10/17 (53%) informative cases of A II and 15/28 (54%) informative cases of A III. LOH on 19q was detected in 2/18 (11%) informative cases of A II and in 12/26 (46%) informative cases of A III. Thus, the majority of chromosomal regions examined in this study do not appear to play a role in malignant progression of astrocytomas. LOH 17p is a frequent event in astrocytoma but has not been detected at a higher incidence in anaplastic variants. However, a putative tumor suppressor gene on chromosome 19q emerges as an interesting novel candidate for a progression-associated gene in human astrocytic gliomas.
开展了一项研究,以检验在胶质瘤中已显示出杂合性缺失的基因座是否参与了从低级别星形细胞瘤到间变性变体的恶性进展过程。我们分析了18例世界卫生组织II级(A II)的高分化星形细胞瘤和26例世界卫生组织III级(A III)的间变性星形细胞瘤,检测其1p、1q、9p、9q、10p、10q、11p、13q、17p、19p、19q和22q染色体上的杂合性缺失(LOH)以及表皮生长因子受体(EGFR)的扩增情况。采用基于聚合酶链反应(PCR)的微卫星重复序列分析法,在银染聚丙烯酰胺凝胶上检测多态性。在18例A II的信息性病例中有1例(6%)出现9p上的LOH,在25例A III的信息性病例中有4例(16%)出现9p上的LOH。在17例A II的信息性病例中有10例(53%)观察到17p上的LOH,在28例A III的信息性病例中有15例(54%)观察到17p上的LOH。在18例A II的信息性病例中有2例(11%)检测到19q上的LOH,在26例A III的信息性病例中有12例(46%)检测到19q上的LOH。因此,本研究中检测的大多数染色体区域似乎在星形细胞瘤的恶性进展中不起作用。17p上的LOH在星形细胞瘤中是常见事件,但在间变性变体中未检测到更高的发生率。然而,19q染色体上一个假定的肿瘤抑制基因成为人类星形细胞胶质瘤中与进展相关基因的一个有趣的新候选基因。