Absence of a functional p53 increases TMZ sensitivity in traditional glioma cell lines, an effect that is independent of MGMT status, and not seen in BTICs.
Because p53 is frequently mutated in brain tumors and the ING1 locus maps to a site of which the loss is associated with gliomas, we analyzed the mutation and expression profiles of ING1B in human brain tumors.
Our results suggest that in pediatric high-grade gliomas: (i) histological grading does not have strong prognostic significance, (ii) YKL-40 overexpression is less frequent than adult high-grade gliomas and does not correlate with a more aggressive behavior, (iii) TP53 mutations but not p53 expression may correlate with a more aggressive behavior, and (iv) IDH1 mutations are absent.
As mutations of the p53 tumor suppressor gene represent an early event in the development of gliomas, we attempted to determine whether both components of gliosarcomas share identical alterations of the p53 gene.
A genomic analysis of the six genes identified in the glioma pathway by cBioPortal indicated that TMZ might exert biological effects via interaction with the tumor protein P53(TP53) signaling axis.
The expression level of MDM4-B mRNA detected by real-time PCR was not only significantly associated with tumor stages, but also with p53 mutation and Ki-67 status which are important clinical molecular markers of glioma.
These results suggest that mutation of the PTEN gene is a later event than that of the p53 gene in glioma progression and is associated with both the genetic pathways.
To our knowledge, this is the first report of an altered p53 gene in a low-grade nonrecurrent glial tumor and highlights the presence of further checks and balances on the control of cell proliferation and other malignancy-associated phenotypes, even in an already-established tumor.
More than 70% of p53 mutations observed during glioma progression are G:C-->A:T transitions, predominantly at CpG sites, i.e. likely to be produced by deamination of 5-mcC or related spontaneous mechanisms.
To analyse the molecular background for that epiphenomenon LN229 glioma cells which harbour a TP53 mutation were transfected with a plasmid encoding p53 wild-type and an angiogenesis protein array was performed.
Induction of apoptosis is one of the mechanisms underlying the effects of chloroquine on suppressing glioma cell growth and viability. siRNA-mediated downregulation of p53 in wild-type but not mutant p53 glioblastoma cells substantially impaired chloroquine-induced apoptosis.
Together, our findings suggest that p48 functions as an oncogene by promoting glioma tumorigenicity via interactions with HDM2 that contribute to p53 downregulation.
This suggested that the p16/p15 and the p53 gene alterations and their combinations in at least some glioma cell lines reflected those in the primary glioma tissues.
In support of the functional interaction between CD24 and p53, in silico analyses reveal that TP53 mutates at a higher rate among glioma and prostate cancer samples with higher CD24 mRNA levels.