Using data from a hospital-based case-control study conducted by the National Cancer Institute between 1994 and 1998, we evaluated risk of glioma (n = 388), meningioma (n = 162), and acoustic neuroma (n = 73) with respect to 12 single nucleotide polymorphisms from 10 genes involved in apoptosis and cell cycle control: CASP8, CCND1, CCNH, CDKN1A, CDKN2A, CHEK1, CHEK2, MDM2, PTEN, and TP53.
The analysis of a multifocal glioma revealed three main aspects: 1) the combined cytogenetic and molecular analysis of this subgroup of glioblastoma multiforme is a suitable tool to gain new perspectives in glioma development, 2) the balanced translocation [t(1;15)(p3?6;q2?5)] might harbor a new genetic marker involved in glioma development, and 3) the pattern of p53 mutation suggests a role of p53 in the progression of malignancy, migration, and growth of this particular primary glioblastoma.
Monolayer cultures of glioma cell lines expressing mutant p53 (U251 and U373) or wild-type p53 (U87 and D54) were infected with Ad-p53 and analyzed by Western blotting.
In order to dissect (i) specific effects of wild-type versus mutant p53, and (ii) transdominant-negative versus gain-of-function effects of mutant p53, we included glioma cell lines with functional wild-type (LN-229), mutant (LN-18) or deleted (LN-308) p53 genes.
Our data suggest that TP53Pro47Ser and Arg72Pro SNPs are not involved either in susceptibility to developing gliomas or in patient survival, at least in the Brazilian population.
We further demonstrate that O(6)MeG-triggered apoptosis requires Fas/CD95/Apo-1 receptor activation in p53 non-mutated glioma cells, whereas in p53 mutated gliomas the same DNA lesion triggers the mitochondrial apoptotic pathway.
Six constitutional missense mutations of the p53 gene were identified (13.6%), but no mutations of the p16 and PTEN genes were found, suggesting that (1) germline p53 mutations contribute to a small portion of astrocytic tumors, (2) inherited mutations of the p16 and PTEN gene do not predispose to the development of gliomas, and (3) other genes are involved in glioma predisposition.
Taken together, these data suggest that activation of the normally antiapoptotic protein NFkappaB does not always necessarily protect cells from apoptosis but, in the glioma cell lines tested so far, and in an environment where p53 is constitutively active, also leads to the induction of cell death.
Polar lipid remodeling and increased sulfatide expression are associated with the glioma therapeutic candidates, wild type p53 elevation and the topoisomerase-1 inhibitor, irinotecan.
These findings suggest that a genetic factor may be responsible for the clustering of glial tumors in this family, but it is unlikely that the genetic alteration is mutation of the p53 gene.
In stratified analyses by ethnicity, source of controls, and glioma subtypes, the p53 codon 72 Arg/Pro polymorphism did not alter the risk for glioma in population-based, hospital-based, astrocytoma, and oligodendroglioma studies among Caucasian.
In this study, mIDH1R132H immunoreactivity in 120 reactive gliosis specimens of various etiologies is compared with Wilms Tumor 1 (WT1) and p53 expression, both markers applied for the differentiation of reactive gliosis and glioma.
In contrast to results in other types of malignant tumors, where up to 40% of patients have high serum titers of p53-aAb, no such antibodies were found in patients with malignant cerebral glioma despite the presence of mutated or alterated p53 protein in the primary tumors.
This indicates that the gene(s) on the 17p13.3 region of the human chromosome may be influencing the p53 immunopositivity status of glial tumors and possibly other tumors in general.
In conclusion, this bioinformatics analysis indicated that DEGs and core genes, such as TP53, might influence the development of glioma, especially in tumor proliferation, which were expected to be promising biomarkers for diagnosis and treatment of glioma.
We previously investigated IDH1/2 and TP53 mutations via Sanger sequencing for adult supratentorial gliomas and reported that PCR-based sequence analysis classified gliomas into three genetic subgroups that have a strong association with patient prognosis: IDH mutant gliomas without TP53 mutations, IDH and TP53 mutant gliomas, and IDH wild-type gliomas.
We analysed p53 and p14arf in relation with five other genetic loci encoding the most frequently mutated genes in human gliomas: cdkn2a, mdm2, egfr, pten and the chromosomal regions 10q23.3 and 10q25-26.
To override the resistance mechanism of glioma cells with p53 mutation to radiation, we transduced U-373MG malignant astrocytoma (glioma) cells harboring mutant p53 with Fas ligand via an adenovirus (Adv) vector in combination with X-ray irradiation, and evaluated the degree of apoptosis.