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

Division of Neuropathology, Department of Pathology I, Sahlgrenska Hospital, S-41345 Gothenburg [G. R., L. L., K. I., E. E. S., V. P. C.], and Ludwig Institute for Cancer Research, Stockholm Branch, S-10401 Stockholm [L. L., V. P. C.], Sweden

The MDM2 (murine double minute 2) gene has recently been shown to code for a cellular protein that can complex the p53 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 alleles on chromosome 17. Our results indicate that amplification and overexpression of MDM2 may be an alternative molecular mechanism by which a subset of human malignant gliomas escapes from p53-regulated growth control.

¹ Supported by grants from the Swedish Cancer Fund and the Inga-Britt and Arne Lundberg foundation.

² G. R. is supported by a postdoctoral fellowship from the Deutsche Forschungsgemeinschaft.

³ To whom requests for reprints should be addressed, at the Department of Pathology I, University of Gothenburg, Sahlgrenska Hospital, S-41345 Gothenburg, Sweden.

Received 4/16/93. Accepted 5/11/93.

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