Gliomas of astrocytic, oligodendroglial and ependymal origin account for more 
than 70% of all brain tumors. The most frequent (65%) and most malignant 
histological type is the glioblastoma. Since the introduction of computerized 
tomography and magnetic resonance imaging, the incidence rates of brain tumors 
have been rather stable, with a tendency of higher rates in highly developed, 
industrialized countries. Some reports indicate that Caucasians have higher 
incidence than black or Asian populations, but to some extent, this may reflect 
socio-economic differences and under-ascertainment in some regions, rather than 
a significant difference in genetic susceptibility. With the exception of 
pilocytic astrocytomas, the prognosis of glioma patients is still poor. Less 
than 3% of glioblastoma patients are still alive at 5 years after diagnosis, 
higher age being the most significant predictor of poor outcome. Brain tumors 
are a component of several inherited tumor syndromes, but the prevalence of 
these syndromes is very low. Several occupations, environmental carcinogens, and 
diet (N-nitroso compounds) have been reported to be associated with an elevated 
glioma risk, but the only environmental factor unequivocally associated with an 
increased risk of brain tumors, including gliomas, is therapeutic X-irradiation. 
In particular, children treated with X-irradiation for acute lymphoblastic 
leukemia show a significantly elevated risk of developing gliomas and primitive 
neuroectodermal tumor (PNET), often within 10 years after therapy. TP53 
mutations are frequent in low-grade gliomas and secondary glioblastomas derived 
therefrom. Approximately 60% of mutations are located in the hot spot codons 248 
and 273, and the majority of these are G:C-->A:T transitions at CpG sites. TP53 
mutations are significantly more frequent in low-grade astrocytomas with 
promoter methylation of the O(6)-methylguanine-DNA methyltransferase repair 
gene, suggesting that, in addition to deamination of 5-methylcytosine, exogenous 
or endogenous alkylation in the O(6) position of guanine may contribute to the 
formation of these mutations.