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.
In this study, we examined the effect of flavopiridol on a panel of glioma cell lines having different genetic profiles: five of six have codeletion of p16(INK4a) and p14(ARF); three of six have p53 mutations; and one of six shows overexpression of mouse double minute-2 (MDM2) protein.
Lack of p16INK4 or retinoblastoma protein (pRb), or amplification-associated overexpression of cdk4 is observed in distinct subsets of malignant glial tumors and cell lines.
Loss of Ink4a-Arf results in increased IGFBP2, which contributes to glioma progression, thereby implicating IGFBP2 as a marker and potential therapeutic target for Ink4a-Arf-deleted gliomas.
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.
Our previous study has shown that inhibitor of differentiation 4 (ID4) dedifferentiates Ink4a/Arf(-/-) mouse astrocytes and human glioma cells to glioma stem-like cells (induced GSCs or iGSCs).
Reactivation of p53 by either gene transfer or pharmacologic approaches may compensate for loss of p19Arf or excess mdm2 expression, common events in melanoma and glioma.
Seven independent chromosomal loci have robustly been associated with glioma risk: 5p15.33 (rs2736100, TERT), 8q24.21 (rs4295627, CCDC26), 9p21.3 (rs4977756, CDKN2A-CDKN2B), 20q13.33 (rs6010620, RTEL1), and 11q23.3 (rs498872, PHLDB1), and two loci at 7p11.2 (rs11979158 and rs2252586, EGFR).
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.
Specific single nucleotides polymorphisms (SNPs) rs4977756 (CDKN2A/B), rs6010620 (RTEL1), rs498872 (PHLDB1), rs2736100 (TERT), and rs4295627 (CCDC26) have been associated with glioma susceptibility and are potential risk biomarkers.
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.
Taken together with the facts that only one PXA preceded E-GBM among these lower-grade lesions, and that co-occurrence of BRAF V600E, TERT promoter mutations and CDKN2A/B homozygous deletions have been reported to be rare in conventional lower-grade diffuse gliomas, the diffuse glioma-like components may be distinct infiltrative components of E-GBM, reflecting intratumoral heterogeneity.
The 18A2/mts1 was expressed in all the cells studied with the exception of fetal brain cells and the low grade non-invasive glioma derived IPRK-7 cell line.
The average percentage of methylation in the promoter region of p14ARF gene in brain samples from glioma patients is 39.4%, while 0 from autopsy donors.
The findings also provide corroborative evidence that CDKN2/p16 and RB are the critical glioma tumor suppressor genes on chromosomes 9p and 13q, respectively.
The genetic variants associated with the risk of glioma in the EGFR gene have also been associated with specific somatic aberrations, including loss at the CDKN2A/B locus and allele specific loss of EGFR in the tumors.
The Investigating and defining if glial tumors with CDKN2A/B and MTAP homozygous loss may be vulnerable to new forms of therapy, namely those affecting the methionine salvage pathway, was proven to be of importance.
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.