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.
A human glioma cell line (U-87MG) that expresses wild-type p53, one that expresses mutant p53 (T-98G), and a T-98G derivative (T-98G/p53) that was transfected with a wild-type p53 expression vector (pCDM8-p53/neo) were used.
A human glioma cell line (A172/mp53) stably transfected with a plasmid containing mutated p53 and a human cervical cancer cell line (HeLa/bcl-2) transfected with a bcl-2 expression plasmid were used.
A series of nine familial gliomas were characterized with 1-megabase resolution BAC array-based comparative genomic hybridization (aCGH) together with germline sequence analysis of TP53.
A significant inverse correlation was observed between expression of miR-141-3p and p53 in glioma and normal brain tissues (R<sup>2</sup>=0.506, P<0.0001).
A systematic screening for p53 mutations in surgical materials from patients with glioma revealed a 378C>G mutation that creates a stop codon at the position of amino acid residue 126.
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.
All but one of the tumours with TP53 mutation showed p53 immunopositivity, but 5 low-grade and 10 high-grade gliomas had p53 protein nuclear accumulation in the absence of detectable mutation. p53 status was unrelated to p21 expression.
Also, we found that linarin-reduced cellular proliferation of glioma was dependent on p53 up-regulation and Nuclear factor kappa-B (NF-κB)/p65-down-regulation, thereby inhibiting glioma cell growth.
Although it remains imperfect, p53 expression with a threshold of 10% is a good surrogate marker for missense TP53 mutations and appears helpful in the setting of LGG phenotype diagnosis.
Although mutation or inactivation of the p53 tumor suppressor gene occurs at early stages in gliomas and is associated with tumor progression, many tumors including high-grade glioblastoma multiforme carry a functionally intact p53 gene.
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.