[The molecular basis of glia-derived tumours of the brain. Part I]

The development and progression of astrocytic tumours is associated with acquisition and accumulation of genetic alternations. Loss of heterozygosity (LOH) on chromosome 17p., p53 mutations and overexpression of the platelet-derived growth factor (PDGF) receptor (chromosome 22q), are the most common detectable changes in astrocytomas (WHO grade II). Anaplastic astrocytomas (WHO grade III) involve LOH on chromosome 19q, deletion of p16 tumor suppressor gene on chromosome 9p and disturbed expression of gene RB on chromosome 13q. LOH on chromosome 10 is restricted largely to glioblastomas (WHO grade IV). This tumour also is characterized by amplification and/or overexpression of gene coding Epidermal Growth Factor Receptor (EGFR) on chromosome 7p. There is growing evidence that two genes encoding triiodothyronine receptors TR alpha [17q21] and TR beta [3p21-p25]) belong also to the group of genes involved in tumorigenesis. Mutations of these genes as well as markedly disturbed expression and function of the encoded proteins were found in tumour tissue. This is supported by facts. that T3 via TRs regulate proliferation, growth, differentiation and apoptosis, the processes that are deeply disturbed in tumour tissue. TRs affects also the action of certain protooncogenes (Mdm2) and tumor suppressors (p53, Rb).