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Amplification and expression of cyclin D genes (CCND1, CCND2 and CCND3) in human malignant gliomas
R Büschges1, R G Weber, B Actor
1Institut für Neuropathologie, Rheinische Friedrich-Wilhelms-Universität, Bonn, Germany.
Abstract:
Malignant gliomas frequently show genetic aberrations of genes coding for cell cycle regulatory proteins involved in the control of G1/S phase transition. These include mutation and/or deletion of the retinoblastoma (RB1) gene, homozygous deletion of the CDKN2A and CDKN2B genes, as well as amplification and overexpression of the CDK4 and CDK6 genes. The D-type cyclins (cyclin D1, D2, and D3) promote cell cycle progression from G1 to S phase by binding to and activating the cyclin dependent kinases Cdk4 and Cdk6. Here, we have investigated a series of 110 primary malignant gliomas and 8 glioma cell lines for amplification and expression of the D-type cyclin genes CCND1 (11q13), CCND2 (12p13), and CCND3 (6p21). We found the CCND1 gene amplified and overexpressed in one anaplastic astrocytoma of our tumor series. Two glioblastomas and one anaplastic astrocytoma showed CCND2 gene amplification, but lacked significant overexpression of CCND2 transcripts. Amplification and overexpression of the CCND3 gene was detected in the glioblastoma cell line CCF-STTG1, as well as in one primary glioblastoma and in the sarcomatous component of one gliosarcoma. Our data thus suggest that amplification and increased expression of CCND1 and CCND3 contribute to the loss of cell cycle control in a small fraction of human malignant gliomas.
Insights
Genetic alterations in D-type cyclin genes (CCND1, CCND2, CCND3) are implicated in malignant gliomas. Amplification and overexpression of CCND1 and CCND3 were observed in a subset of gliomas, contributing to cell cycle dysregulation.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Malignant gliomas often exhibit genetic alterations in cell cycle regulators controlling the G1/S phase transition.
- Genes like RB1, CDKN2A, CDKN2B, CDK4, and CDK6 are frequently affected.
- D-type cyclins (cyclin D1, D2, D3) are crucial for G1 to S phase progression by activating cyclin-dependent kinases Cdk4 and Cdk6.
Purpose of the Study:
- To investigate the amplification and expression of D-type cyclin genes (CCND1, CCND2, CCND3) in malignant gliomas.
- To determine the role of these genes in the loss of cell cycle control in gliomas.
Main Methods:
- Analysis of gene amplification and transcript expression for CCND1, CCND2, and CCND3.
- Study included 110 primary malignant gliomas and 8 glioma cell lines.
Main Results:
- CCND1 gene amplification and overexpression found in one anaplastic astrocytoma.
- CCND2 gene amplification detected in two glioblastomas and one anaplastic astrocytoma, without significant overexpression.
- CCND3 gene amplification and overexpression observed in a glioblastoma cell line, one primary glioblastoma, and a gliosarcoma component.
Conclusions:
- Amplification and increased expression of CCND1 and CCND3 contribute to cell cycle dysregulation in a subset of human malignant gliomas.
- These findings highlight the potential role of D-type cyclins in glioma pathogenesis.