1.Dipartimento Di Medicina, Chirurgia E Odontoiatria, Polo Universitario San Paolo, Genetica Medica, Via di Rudini, 8, 20142 Milano, Italy
- Giant cell glioblastoma
- Clear Cell
No underlying cause has been identified for the majority of malignant gliomas. Epidemiologic factors including specific occupational exposures, environmental carcinogens, foods containing N-nitroso compounds, electromagnetic fields, etc. have been associated to only a small proportion of gliomas. The only two firmly established factors of primary brain tumors are the exposure to high doses of ionizing radiation and inherited mutations of highly penetrant genes associated with rare syndromes (Table 3).
In addition, preliminary evidence points to a lower glioma risk among people with allergic conditions and high levels of serum IgE. Polymorphisms of genes that affect detoxification, DNA repair, and cell-cycle regulation have also been implicated in the development of gliomas.Recently, two international Brain Tumor consortia have been formed: the Brain Tumor Epidemiology Consortium (BTEC)( http://epi.grants.cancer.gov/btec/ ) to identify potential genetic and environmental risk factors and the GLIOGENE to study the genetic basis of familial gliomas.
There is growing evidence that glioma stem cells may contribute to the resistance of malignant gliomas to standard treatments. Radioresistance in stem cells generally results from the preferential activation of DNA-damage-response pathways, whereas chemoresistance results partly from the overexpression of O6-methylguanine-DNA methyltransferase (MGMT), the up-regulation of multidrug resistance genes, and the inhibition of apoptosis. Therapeutic strategies that effectively target stem cells sparing normal cells and overcome their resistance to treatment will be necessary if malignant gliomas are to be completely eradicated. Another determined obstacle to effective therapy is the invasive nature of glioma cells into the surrounding brain.
1p/19q lossDeletions of 1p and 19q are associated with tumors with oligodendroglial components. Combined alterations have been observed in up to 70% of oligodendrogliomas and 50% of mixed oligoastrocytomas. Besides being a relevant diagnostic marker, 1p/19q loss has been recently validated for its prognostic relevance by prospective data suggesting that 1p /19q deletion is predictive of radio-chemosensitivity in anaplastic oligodendroglial tumors and mixed oligoastrocytomas. Based on the observation that the majority of 1p and 19q deletions seem to involve the entire 1p and 19q arms, in a recent paper Jenkins RB et al showed that an unbalanced t(1;19)(q10;q10) underlies the formation of the combined 1p and 19q deletion in gliomas and in addition it predicts a better prognosis of patients with oligodendroglioma.
The major signalling pathways involved in the pathogenesis of glioblastomas are depicted in Figure 3 and then shortly commented.
Nervous System: Glioma: an overview
Atlas Genet Cytogenet Oncol Haematol. 2008-08-01
Online version: http://atlasgeneticsoncology.org/solid-tumor/5763/nervous-system-glioma-an-overview