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Laboratory of Molecular Neuro-Oncology, Department of Neurosurgery, Emory University School of Medicine, Atlanta, Georgia 30322 [J. H., J. R. A., C. D. J.]; Department of Pathology, Karolinska Hospital, and Ludwig Institute for Cancer Research, Stockholm Branch, S-10401 Stockholm, Sweden [V. P. C.]; and Radiobiology Program, Department of Radiation Oncology [M. J. A-T.] and Molecular Oncology Program [R. G., R. S. D.], Cross Cancer Institute, Edmonton, Alberta, Canada T6G 2G3
Recently, it has been shown that a gene encoding the cyclin-dependent kinase 4 inhibitory protein, p16, is frequently targeted for homozygous deletions in several types of tumor cell lines, including those established from malignant gliomas. Here we have examined 32 glioma cell lines for amplification-associated overexpression of the CDK4 gene as an alternative mechanism for abrogating the growth-regulatory effects of p16. Two of the cell lines revealed high-level expression of CDK4 in association with gene amplification, and this alteration was observed among the 10 cases having intact p16 genes. Consequently, 24 of 32 glioma cell lines revealed one of two alternative genetic alterations, each of which indicates that increased cdk4 kinase activity is important to glial tumor development.
1 This work was supported by grants from the National Cancer Institute (CA55728), the Swedish Cancer Society, and the National Cancer Institute of Canada, and by generous gifts from the Brain Tumor Foundation for Children of Georgia.
2 To whom requests for reprints should be addressed, at Department of Neurosurgery, Emory University School of Medicine, 1327 Clifton Rd., NE, Atlanta, GA 30322.
Received 9/ 2/94. Accepted 10/ 5/94.
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