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Analysis of the p21 gene in gliomas
Y J Li1, K Hoang-Xuan, X P Zhou
1INSERM U434, Génétique des Tumeurs, CEPH, Paris, France.
Abstract:
The p21 gene encodes a cyclin dependent kinase inhibitor protein (p21) which has a tumor suppressive activity in a variety of tumor cell lines. Since, the p21 gene is up-regulated by the p53 tumor suppressor gene, which is frequently mutated in gliomas, acting therefore in the same control pathway, it constitutes a good candidate gene to be also inactivated in these tumors. To test this hypothesis, DNAs from 81 gliomas (48 glioblastomas, 11 anaplastic astrocytomas, 10 low-grade astrocytomas, 12 oligodendrogliomas and mixed gliomas), were investigated for mutations in the p21 coding sequence by denaturant gradient gel electrophoresis followed by sequencing. All these tumors have been previously screened for p53 mutations. Three different DNA variants were identified on codon 31 (17 cases), 27 (1 case) and 117 (1 case) and shown to be also present in matching constitutional DNA, suggesting they were polymorphisms. None of the tumors demonstrated a somatic mutation. No significant correlation between the presence of a p21 variant and the p53 mutation tumor status was observed. In conclusion, mutation in the p21 gene unlikely contributes to the development of gliomas.
Insights
Mutations in the p21 gene, which inhibits tumor growth, are unlikely to cause gliomas. Researchers found only polymorphisms, not somatic mutations, in p21 across 81 glioma samples.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The p21 gene encodes a protein with tumor-suppressive activity.
- p21 is upregulated by the p53 tumor suppressor gene, frequently mutated in gliomas.
- This suggests p21 inactivation could contribute to glioma development.
Purpose of the Study:
- To investigate mutations in the p21 gene in various glioma types.
- To determine if p21 gene mutations correlate with p53 mutation status in gliomas.
Main Methods:
- DNA analysis of 81 gliomas (glioblastomas, astrocytomas, oligodendrogliomas, mixed gliomas).
- Investigated p21 coding sequence for mutations using denaturing gradient gel electrophoresis and sequencing.
- Compared p21 findings with prior p53 mutation screening.
Main Results:
- Identified three DNA variants in p21 (codons 31, 27, 117).
- These variants were present in constitutional DNA, indicating they are polymorphisms, not somatic mutations.
- No somatic mutations in the p21 gene were found in any glioma samples.
- No significant correlation observed between p21 variants and p53 mutation status.
Conclusions:
- Somatic mutations in the p21 gene are unlikely to play a role in glioma development.
- The p21 gene's tumor-suppressive function does not appear to be compromised by mutation in this cancer type.