[Molecular genetics of gliomas]

Gliomas represent the majority of primary central nervous system tumors in adults. The moderate overall impact of conventional therapeutic regimens on these inherently aggressive neoplasms raises the need for a direct intervention in the biology of neoplastic change. In the last decade important achievements in the molecular genetic basis of deregulated cell-cycle have been brought about, the neuro-oncologic implications of which are reviewed here. Loss of equilibrium between promoting factors and negative control of mitosis emergeus as a general principle, with gene amplification-overexpression operating in the former group, while deletions, loss of function-type mutations and post-transcriptional events prevail at the opposite pole. Damage to regulatory mechanisms will result, as a major consequence, in transgression of one or more of the so-called restriction points of the cell-cycle. Lesions of the genome are further ramified by supracellular processes involving autocrine and paracrine growth-stimulating loops. Malignant progression of gliomas, therefore, can be envisaged as a cumulative sequence of genetic alterations and interactions of tumor cells with their microenvironment.