AMPLIFICATION OF THE CYCLIN-DEPENDENT KINASE-4 (CDK4) GENE IS ASSOCIATED WITH HIGH CDK4 PROTEIN-LEVELS IN GLIOBLASTOMA-MULTIFORME

Genetic alterations on the long arm of chromosome 12, including both g ene amplification and allelic loss, are associated with malignant prog ression of human gliomas. The region of the chromosomal arm 12q that i s amplified in malignant gliomas contains the CDK4 gene, a cell cycle regulatory gene which promotes cell division. To evaluate the frequenc y 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 glioma s, meningiomas, medulloblastomas and metastatic carcinomas (only 6 of 274 cases). There was no correlation between CDK4 gene amplification a nd allelic loss of chromosome 12. To assess the significance of CDK4 g ene 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 expr ession levels, whereas no increased cdk4 expression was seen in gliobl astomas without CDK4 gene amplification. These data support the functi onal activity of CDK4 gene amplification in glioblastoma multiforme an d point to an important role of CDK4 gene amplification in a subset of glioblastomas.