Amplification of the cyclin-dependent kinase 4 (CDK4) gene is associated with high cdk4 protein levels in glioblastoma multiforme

Abstract

Genetic alterations on the long arm of chromosome 12, including both gene amplification and allelic loss, are associated with malignant progression of human gliomas. The region of the chromosomal arm 12q that is amplified in malignant gliomas contains the CDK4 gene, a cell cycle regulatory gene which promotes cell division. To evaluate the frequency of CDK4 gene amplification, we analyzed a series of 355 brain tumors using a quantitative non-radioactive polymerase chain reaction assay. CDK4 gene amplification occurred in 9 of 81 glioblastomas (11%), but was rare in other neoplasms, including low-grade and anaplastic gliomas, meningiomas, medulloblastomas and metastatic carcinomas (only 6 of 274 cases). There was no correlation between CDK4 gene amplification and allelic loss of chromosome 12. To assess the significance of CDK4 gene amplification, we analyzed protein extracts from 37 glioblastomas by Western blotting with a commercially available polyclonal antibody to cdk4. All tumors with CDK4 gene amplification showed high cdk4 expression levels, whereas no increased cdk4 expression was seen in glioblastomas without CDK4 gene amplification. These data support the functional activity of CDK4 gene amplification in glioblastoma multiforme and point to an important role of CDK4 gene amplification in a subset of glioblastomas.