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Mutation rate of the CDKN2 gene in malignant gliomas
1Istituto Nazionale Neruologico C. Besta, Divisione di Biochimica e Genetica, Milan, Italy.
Abstract:
The CDKN2 gene encodes p16, a protein controlling the cell cycle. CDKN2 is deleted in a relevant number of tumor cell lines, but results of the studies in primary tumors are contradictory. We have investigated by using quantitative polymerase chain reaction and single-strand conformation polymorphism analysis the structure of exon 2 of CDKN2 in 32 malignant gliomas. In 11 tumors the amount of amplified material was 21% of that of controls and in 8 tumors it was 42.3%, suggesting the presence of homozygous and hemizygous deletions of the CDKN2 gene, respectively. However, no abnormality could be detected by single-strand conformation polymorphism analysis. The data confirm in primary gliomas that homozygous deletions are a mechanism of CDKN2 inactivation and suggest that another gene in the vicinity could be targeted by mutations.
Insights
Homozygous deletions of the CDKN2 gene, which encodes cell cycle regulator p16, inactivate this tumor suppressor in primary malignant gliomas. This study confirms homozygous deletions as a mechanism of CDKN2 inactivation in gliomas.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The CDKN2 gene encodes the p16 protein, a critical cell cycle regulator.
- CDKN2 deletions are observed in tumor cell lines, but findings in primary tumors are inconsistent.
- Investigating CDKN2 alterations in malignant gliomas is crucial for understanding tumor development.
Purpose of the Study:
- To investigate the structural alterations of the CDKN2 gene, specifically exon 2, in primary malignant gliomas.
- To determine the frequency and type of CDKN2 deletions (homozygous vs. hemizygous) in malignant gliomas.
- To elucidate the role of CDKN2 inactivation in glioma pathogenesis.
Main Methods:
- Quantitative polymerase chain reaction (qPCR) was employed to assess gene dosage.
- Single-strand conformation polymorphism (SSCP) analysis was used to detect structural abnormalities.
- The study analyzed DNA from 32 primary malignant glioma samples.
Main Results:
- Evidence of homozygous deletions (21% reduction in amplified material) was found in 11 tumors.
- Evidence of hemizygous deletions (42.3% reduction in amplified material) was detected in 8 tumors.
- No abnormalities were identified using single-strand conformation polymorphism analysis, indicating deletions were the primary mechanism.
Conclusions:
- Homozygous deletions are confirmed as a mechanism for CDKN2 inactivation in primary malignant gliomas.
- These findings highlight the importance of CDKN2 alterations in glioma development.
- The results suggest that other genes located near CDKN2 may also be targeted by mutations in gliomas.