[Mechanisms of molecular development of human glioma]

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.