**6. Conclusion**

After a detailed review of the literature about the role of the *TP53* gene in the genesis and development of CNS tumors we can conclude that both genetic and epigenetic alterations that inactivate this gene are directly related to these phenomena in specific histopathological tumors. In addition, several studies have investigated the predictive value of *TP53* mutation status and have shown that specific types of genetic mutations can alter the function and expression of p53, influencing tumor response to treatment and patient outcome, revealing thus to be a useful prognostic tool. Genetic alterations in the p53 pathway are early events in the molecular pathogenesis of diffuse astrocytoma and the highest frequencies of allelic loss and/or mutation of *TP53* gene are mostly seen in gliomas, and are a genetic hallmark of: lowgrade diffuse astrocytomas (> 60%), mainly in gemistocytic astrocytomas that carry *TP53* mutations in up to 80% of the cases; anaplastic astrocytomas (40-70%); secondary glioblastoma (>65%); oligoastrocytomas (~40%). Genetic *TP53* mutations are rarely found or seen less frequently in other CNS tumors, however, some studies have shown that some changes have found important prognostic value. Recently, our group investigated the presence of numerical aberrations of chromosome 17 and *TP53* in 5 subjects with brain metastasis from breast cancer using dual-color fluorescence in situ hybridization experiments. Deletion of *TP53* was the most frequent alteration observed, suggesting that if this alteration is present in the primary tumors, breast tumors with loss of *TP53* copies have a poorer prognosis and a higher chance for metastasis [237].

Epigenetic events in *TP53* gene has been increasingly recognized as an alternative mechanism for inactivation of function of a tumor suppressor gene. Although less frequently, *TP53* epigenetic abnormalities has been found in CNS tumors and several reports shed light on the involvement of mainly DNA methylation and miRNAs in the p53 pathway, suggesting that this process can be involved in the genesis and progression of these tumors. Clearly, additional studies can provide important insights into the central roles of miRNAs in the p53 pathway, as well as *TP53* promoter methylation, which may provide a route to therapeutic intervention in CNS tumors.

Due the difficulty to the use of traditional therapeutic modalities such as chemotherapy and radiotherapy in the CNS tumors, especially in high grade tumors, such as glioblastomas, , it is expected that in a near future molecular treatment that could be obtain more effective control of disease progression will be used, resulting in an improved clinical course of these patients. Over the years, with the increasing advances of molecular biology techniques, much informa‐ tion has been obtained on the role of p53 in carcinogenesis. Because of the critical role p53 plays in a variety of cancers, a diversity of approaches have been undertaken to target p53 and its altered signaling pathways. Different drugs targeting the p53 system in order to activate the p53 pathway have been developed and several are now in clinical trials, and have shown promising results.
