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Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
Methylation of p14(ARF) gene in meningiomas and its correlation to the p53 expression and mutation
Vishwa Jeet Amatya1, Yukio Takeshima, Kouki Inai
1Department of Pathology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan. vjamatya@mac.com
Abstract:
We have previously reported the statistically significant correlation of immunohistochemical expression of MIB-1 and p53 proteins among benign, atypical, and anaplastic meningiomas and p53 protein expression was high in atypical and anaplastic meningiomas. In the present study, we analyzed 22 cases of meningiomas for mutation of p53 gene in its spectrum of exon 5 to 8 using automated genetic analyzer. We did not find any mutation of p53 in any of these cases, thus suggesting the p53 protein expression is wild type. We analyzed 72 cases of meningiomas for determining the methylation status of p14(ARF) gene and the immunohistochemical expression of MDM2 protein to explain p53 protein expression in these meningiomas. We found methylation of p14(ARF) gene in five of 58 cases of benign meningiomas (8.6%), two of 10 cases of atypical meningiomas (20%), and two of four cases of anaplastic meningiomas (50%). In absence of p53 gene mutation, the high percentage of p14(ARF) gene methylation in high-grade meningioma may have been responsible for accumulation of wild-type p53 protein. In addition, we also found the loss of MDM2 protein in high-grade meningiomas. These deregulations of p14-MDM2-p53 pathway may contribute to the malignant progression of meningioma.
Insights
High-grade meningiomas show p14(ARF) gene methylation and loss of MDM2 protein, leading to wild-type p53 accumulation. This deregulation of the p14-MDM2-p53 pathway may drive meningioma progression.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Previous studies indicated a correlation between MIB-1 and p53 protein expression in meningiomas, with higher p53 levels in atypical and anaplastic types.
- Meningiomas are tumors arising from the meninges, with varying degrees of malignancy.
Purpose of the Study:
- To investigate p53 gene mutations in meningiomas.
- To determine the methylation status of the p14(ARF) gene and MDM2 protein expression in meningiomas.
- To elucidate the mechanisms behind wild-type p53 protein accumulation in high-grade meningiomas.
Main Methods:
- Analysis of p53 gene mutations (exons 5-8) using an automated genetic analyzer in 22 meningioma cases.
- Assessment of p14(ARF) gene methylation status and MDM2 protein expression via immunohistochemistry in 72 meningioma cases.
- Correlation of genetic and protein expression data with meningioma grade.
Main Results:
- No p53 gene mutations were detected in any of the 22 analyzed meningiomas, suggesting wild-type p53 protein.
- p14(ARF) gene methylation was observed in 8.6% of benign, 20% of atypical, and 50% of anaplastic meningiomas.
- Loss of MDM2 protein expression was found in high-grade meningiomas.
Conclusions:
- p14(ARF) gene methylation, in the absence of p53 mutations, likely contributes to the accumulation of wild-type p53 protein in high-grade meningiomas.
- The observed deregulation of the p14-MDM2-p53 pathway may play a role in the malignant progression of meningiomas.
- Further research into the p14-MDM2-p53 pathway could reveal therapeutic targets for meningioma treatment.
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