Amplification and expression of cyclin D genes (CCND1, CCND2 and CCND3) inhuman malignant gliomas

Malignant gliomas frequently show genetic aberrations of genes coding for c ell cycle regulatory proteins involved in the control of G1/S phase transit ion. These include mutation and/or deletion of the retinoblastoma (RB1) gen e, homozygous deletion of the CDKN2A and CDKN2B genes, as well as amplifica tion and overexpression of the CDK4 and CDK6 genes. The D-type cyclins (cyc lin D1, D2, and D3) promote cell cycle progression from G1 to S phase by bi nding to and activating the cyclin dependent kinases Cdk4 and Cdk6, Here, w e have investigated a series of 110 primary malignant gliomas and 8 glioma cell lines for amplification and expression of the D-type cyclin genes CCND 1 (11q13), CCND2 (12p13), and CCND3 (6p21), We found the CCND1 gene amplifi ed and overexpressed in one anaplastic astrocytoma of our tumor series. Two glioblastomas and one anaplastic astrocytoma showed CCND2 gene amplificati on, but lacked significant overexpression of CCND2 transcripts. Amplificati on and overexpression of the CCND3 gene was detected in the glioblastoma ce ll line CCF-STTG1, as well as in one primary glioblastoma and in the sarcom atous component of one gliosarcoma. Our data thus suggest that amplificatio n and increased expression of CCND1 and CCND3 contribute to the loss of cel l cycle control in a small fraction of human malignant gliomas.