Schlegel U
Neurologische Universitätsklinik Bonn.
Nervenarzt. 1993 Aug;64(8):485-93.
Malignant gliomas present a difficult therapeutic problem. Within the last ten years, however, some of the molecular mechanisms have been disclosed that are involved in brain tumour development. According to these results the occurrence of a malignant tumour cell is the result of a multistage process, which involves mutations in several genes. These mutations affect genes regulating cellular proliferation and differentiation, which are called protooncogenes and tumour-suppressor genes (anti-oncogenes). Critical alterations in the proteins encoded by these genes may lead to uncontrolled cell proliferation. In astrocytic gliomas mutations of the tumour suppressor gene p53 are common; mutations of the c-erbB gene, encoding the Epidermal Growth Factor receptor (EGF-receptor), frequently affect glioblastomas. The vast majority of glioblastomas show deletions or loss of a copy of chromosome 10. Anaplastic astrocytomas, glioblastomas and oligodendrogliomas frequently carry deletions in one copy of the chromosome 9q and 19q region, respectively. Allelic loss of these regions suggest the presence of a tumour-suppressor gene on these chromosomal loci and a pathogenetic role of anti-oncogene allelic loss in brain tumour development. Molecular studies provide insight into the pathogenesis of brain tumour development. However, they may also have an impact on developing new forms of tumour-specific therapy. The efficacy of such therapeutic strategies is currently being evaluated in clinical studies.
恶性胶质瘤带来了一个棘手的治疗难题。然而，在过去十年中，一些参与脑肿瘤发生发展的分子机制已被揭示。根据这些研究结果，恶性肿瘤细胞的出现是一个多阶段过程的结果，这一过程涉及多个基因的突变。这些突变影响调控细胞增殖和分化的基因，即原癌基因和肿瘤抑制基因（抗癌基因）。这些基因编码的蛋白质发生关键改变可能导致细胞不受控制地增殖。在星形细胞胶质瘤中，肿瘤抑制基因p53的突变很常见；编码表皮生长因子受体（EGF受体）的c-erbB基因的突变则常常影响胶质母细胞瘤。绝大多数胶质母细胞瘤显示10号染色体缺失或丢失一个拷贝。间变性星形细胞瘤、胶质母细胞瘤和少突胶质细胞瘤分别经常在9号染色体q臂和19号染色体q臂区域出现一个拷贝的缺失。这些区域的等位基因缺失提示这些染色体位点上存在肿瘤抑制基因，以及抗癌基因等位基因缺失在脑肿瘤发生发展中的致病作用。分子研究为脑肿瘤发生发展的发病机制提供了深入了解。然而，它们也可能对开发新的肿瘤特异性治疗形式产生影响。目前正在临床研究中评估此类治疗策略的疗效。
