Amplification and Overexpression of the MDM2 Gene in a Subset of Human Malignant Gliomas without p53 Mutations1

The MDM2 (murine double minute 2) gene has recently been shown to code for a cellular protein that can complex thep53 tumor suppressor gene product and inhibit its function. We studied a series of 157 primary brain tumors and report here that the MDM2 gene is amplified and overexpressed in 8-10% of glioblastomas and anaplastic astrocytomas. Thus, MDM2 represents the second most frequently amplified gene after the epidermal growth factor receptor gene in these tumor types. Sequencing of the p53 transcripts in the cases with MDM2 amplification revealed no mutations and restriction fragment length polymorphism analysis showed, with one exception, no losses of alÃ-eleson chromosome 17. Our results indicate that amplification and overexpression of MDM2 may be an alter native molecular mechanism by which a subset of human malignant gliomas escapes from /753-regulated growth control.