Genetics Of Neuroepithelial Brain Tumours

Abstract

Various etiologies, such as chemical carcinogens and oncogenic viruses, have been postulated to be important in the development of neuroepithelial brain tumours. However, their exact pathogenesis remains unknown and the influence of genetic factors is uncertain. A possible relationship between genetic factors and cerebral tumour development has been under discussion since as early as 1896 when Besold reported two sisters suffering from brain tumours (1). Koch in 1954 thought two factors at least necessary for the formation of a “glioma”: 1. a local hereditary influence: neuroglial dysplasia in the region of the ventricular germinal centres with a tendency to tumour degeneration; he suggested a mutation in a pleiotropic gene to be responsible for this local disturbance. 2. a second or several factors, exogenous or endogenous, that initiate oncogenesis in these predisposed areas (2). This corresponds with the two-hit hypothesis later put forward by Knudson which supposes that cancer results from at least two events one of which could be transmitted genetically (3). In the hereditary forms of cancer, the first mutation occurs in a germinal cell and somatic mutations later occur at the same site, converting proto-oncogenes to oncogenes.