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Department of Pathology, Sahlgrenska Hospital, S-41345 Gothenburg, Sweden [G. R., J. R., K. I., V. P. C.]; National Institute of Health, National Center for Human Genome Research, Bethesda, Maryland 20892 [P. S. M.]; Department of Neuropathology, Heinrich-Heine-University, D-40225 Düsseldorf, Germany [G. R., J. R.]; and Ludwig Institute for Cancer Research, Stockholm Branch and Department of Pathology, Karolinska Hospital, S-17176 Stockholm, Sweden [V. P. C.]
We have investigated 234 tumors of the central nervous system for amplification of 9 different loci from 12q13-14 and report that about 15% of the anaplastic astrocytomas and glioblastomas show amplification at this chromosomal region. The genes most frequently amplified were CDK4 and SAS (18 of 19 cases). MDM2 was coamplified with CDK4 and SAS in 11 tumors while one glioblastoma showed only MDM2 amplification. Some amplicons additionally included GADD153 (9 cases), GLI (6 cases), A2MR (3 cases), and the anonymous locus D12S8 (2 cases). Either MDM2 or CDK4 and SAS showed the highest amplification level in each individual amplicon and amplification of these genes was consistently accompanied by strong overexpression. Our results thus suggest CDK4, SAS, and MDM2 as main targets for the amplification; however, the possibility exists that all amplicons share a common amplified region between MDM2 and CDK4/SAS which might contain one or more as yet unidentified genes.
1 Supported by grants from the Swedish Cancer Fund, the Child Cancer Foundation of Sweden, the Inga-Britt and Arne Lundberg Foundation, the Assar Gabrielssons Fund, and the Stiftelsen Jubileumsklinikens Research Fund.
2 Supported by a postdoctoral fellowship from the Deutsche Forschungsgemeinschaft.
3 To whom requests for reprints should be addressed, at Department of Pathology, Karolinska Hospital, S-17176 Stockholm, Sweden.
Received 6/ 1/94. Accepted 6/22/94.
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