Gliomas

Gliomas are thought to arise from the glial cells of brain tissue. The spectrum of tumours varies with age, implying that cells in a particular state of development are a prerequisite for the occurrence of some tumour types. Premalignant states are not recognized, so we know little about the earliest events in oncogenesis. However, progression of gliomas has been examined by studying large series of tumours of different malignancy grades and by following cases where the tumour is of low malignancy grade at first diagnosis and recurs later as a tumour of higher malignancy grade. When considering premalignant states we can only extrapolate from our knowledge of progression from the least to the most malignant tumour forms. The best studied variants are the astrocytic tumours. There are no consistent genetic aberrations known to characterize the most benign variant of astrocytoma, the pilocytic astrocytoma (malignancy grade I), which occurs mainly in children. Astrocytomas (malignancy grade II) show loss of alleles at 13q, 17p and 22q and occur mainly in early middle age. Loss of one TP53 allele (17p) is associated with mutation of the remaining allele. Loss of one RB1 allele is not. Anaplastic astrocytomas (malignancy grade III) have in approximately 50% of cases aberrations of genes coding for proteins involved in the control of entry into the S phase of the cell cycle, as well as other genetic defects affecting unknown genes. The greatest number of genetic abnormalities is seen in glioblastomas (malignancy grade IV), which have a peak incidence in late middle age. Around 80% of glioblastomas can be shown to have genetic alterations resulting in aberrant control of progression from G1 to the S phase of the cell cycle, and many show amplification of growth factor receptor genes as well as other abnormalities. The bewildering number of genetic anomalies becomes intelligible as we discover that different components of the same cellular control mechanisms are being targeted in individual tumours resulting in a similar phenotype.