Frequency variations in the methylated pattern of p73/p21 genes and chromosomal aberrations correlating with different grades of glioma among south Indian population
Abstract
Gliomas are the most common primary brain tumors in India. The main epigenetic modification in glioma is aberrant DNA methylation that is now renowned to be a common hallmark of brain tumors. This study was designed to determine the frequency of aberrant CpG island methylation in the promoter regions of p21 and p73 in different grades of glioma and to explore their respective chromosomal aberrations. Total of 160 patients with histologically confirmed grades of glioma (I, II, III, and IV) were included in the study. DNA samples from blood and brain tissues, including benign lesions were subjected to sodium bisulfite conversion and hypermethylation detection using methylation-specific PCR followed by RT-PCR. Western blotting was also carried out for p21 and its related protein, p53. A total of 124 of 160 glioma samples (77.5%) displayed CpG island hypermethylation of both p73, p21 genes associated with the loss of mRNA expression (P < 0.001) and the loss of protein expressions (p53 independent p21 expression). p73 gene showed increased methylation frequency in all grades, 40 of 60 (66%) glioblastomas and 16 of 30 (53.3%) anaplastic astrocytoma, 10 of 20(50%) oligodendrogliomas, 8 of 20 (40%) ependymoma, and low-grade glioma 6 of 20 (30%). The percentage of methylation significantly well correlated with the overall survival and also with chromosomal loss. Thus, the studied glioma patients among south Indians showed a high frequency of aberrant methylation with varied chromosomal signatures in different grades, playing a role in aggressiveness and characterization of a particular grade, the appreciation of which might help for designing a specific therapy.
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Methylation of the promoter regions of TP63 and TP73 corresponded with higher grade glioblastoma.
“Indeed, methylation of the promoter regions of TP63 and TP73 corresponded with higher grade GBM [104].”
From The p53 Pathway in Glioblastoma (2018) · cites this paper as [104]
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- Authors
- Palani, M., Devan, S., Arunkumar, R., & Vanisree, A. J.
- Affiliations
- University of Madras (IN)
- Madras Medical College (IN)
- Corresponding author
- Vanisree, A. J.
- Venue
- Medical Oncology
- Published
- 2010-09-16
- Volume
- 28
- Issue
- S1
- Pages
- 445-452
- ISSN
- 1357-0560 (ISSN-L)
- 1559-131X
- OpenAlex
- W2080979530
- Cited by
- 10
- References
- 26
- Citations by year
- 2022: 1 · 2021: 1 · 2018: 1 · 2016: 2 · 2015: 1 · 2014: 2 · 2013: 1 · 2012: 1
- FWCI
- 0.28
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Medical Oncology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer-related molecular mechanisms research
- Keywords
- glioma, DNA methylation, p73, p21, CpG island hypermethylation, promoter hypermethylation, glioma grade, chromosomal abnormalities, glioblastoma, anaplastic astrocytoma, oligodendroglioma, ependymoma, p53, South Indian population
- MeSH terms
- Tumor Protein p73, Adolescent, Adult, Aged, Brain Neoplasms, Chromosome Aberrations, DNA-Binding Proteins, Female, Glioma, Humans, India, Male, Middle Aged, Nuclear Proteins, Genetic Variation, Gene Expression Regulation, Neoplastic, DNA Methylation, Tumor Suppressor Proteins, Cyclin-Dependent Kinase Inhibitor p21, Young Adult, Neoplasm Grading
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