Molecular genetics and tumour suppressor genes in gliomas

In astrocytic gliomas, which are the most common cerebral neoplasms, loss of p53 gene function appears to be an early event associated with malignant transformation. Further p53 mutations, loss of chromosome 10, abnormalities of the p16 gene, Rb gene, and amplification of the EGFR gene are late events associated with progression of anaplastic astrocytoma to the most malignant form of glioma, glioblastoma multiforme. A direct pathway from normal glia to the most malignant glioma the glioblastoma multiforme is also possible, and is associated with losses of chromosome 10 portions and subsequent amplification of the EGFR gene. Abnormalities of the RB/p16 may also play a role in this pathway but they are not yet clearly defined. Less well-defined abnormalities are associated with oligodendrogliomas or mixed gliomas and include chromosome 1p and 19q abnormalities.