The median methylation level of MGMT in glioma samples was 64.65% (IQR, 54.87%-74.37%) compared to 38.30% (IQR, 34.13%-45.45%) in healthy controls, and all revealed significant differences including P16.
These findings show that CDKN2 p16 540 C>G, CDKN2 p16 580 C>T and MDM2 SNP309 T>G variants and their haplotypes may be risk factors for the development of primary brain tumors, especially of glioma.
In this study, we analyzed the deletion status of all three exons of p16 and frequency of exon 2 somatic point mutations in glioma from the Indian population and its clinical implications.
Our previous studies demonstrated that downregulation of uPAR expression and restoration of p16 regress glioma growth in nude mice and downregulate alphavbeta3 integrin receptor expression.
Combined evaluation by single clone and whole chromosome analysis plus 'moving average (MA) approach' enabled us to confirm most of the genetic abnormalities previously identified to be associated with glioma progression, including +1q32, +7, -10, -22q, PTEN and p16 loss, and to disclose new small genomic regions, some correlating with grade malignancy.
We expected that downregulation of uPAR and overexpression of p16 using a bicistronic vector might cause a additive and cooperative effect in the suppression of glioma invasion and growth.
The results suggest that LOH on 9p and p16 deletions may prove to be objective standards for the diagnosis of patients with high-grade gliomas, although the absence of these abnormalities is nonprognostic.
To determine the roles of p16 alterations in glioma formation, we have established ecdysone-driven inducible p16 expression in the human glioblastoma cell line CL-4, which were derived from p16-null U87MG cells.
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.
These findings indicate that the p16 gene plays an important role in the regulation of glioma angiogenesis, suggesting a novel function of the p16 gene.
These results might suggest that deletion of p16 genes promoted unrestrained growth in human glioma but has no relationship to the chemosensitivity to CDDP, ACNU and AZC.
Structural alterations in the p16INK4 gene were examined in early passage human glioma cell lines and related to the expression of p16 transcripts and protein.
These results suggest that p16/CDKN2 inactivation is a significant factor in the genesis and progression of gliomas and that the restoration of the wild-type p16 protein could have clinical and therapeutic utility.
Here we have examined 32 glioma cell lines for amplification-associated overexpression of the CDK4 gene as an alternative mechanism for abrogating the growth-regulatory effects of p16.