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Replacement of the p16/CDKN2 Gene Suppresses Human Glioma Cell Growth¹

Ludwig Institute for Cancer Research [W. A., R. N., F. B. F., W. K. C., H-J. S. H.], Department of Medicine [W. K. C., H-J. S. H.], and Center for Molecular Genetics [W. K. C.], University of California, San Diego, La Jolla, California 92093-0660, and Cancer Biology Program, Stanford University, Stanford, California 94305 [W. A.]

The p16/CDKN2 gene has many features of a growth suppressor gene: it maps to 9p21, a frequent region of loss of heterozygozity in a variety of tumor types; it encodes an inhibitor of cyclin-dependent kinase 4; and its homozygous deletion is common in tumor-derived cell lines. However, the lower frequency of alteration of the gene in primary tumor tissue as compared to the cognate tumor cell lines has brought this interpretation into question. We have assessed the growth suppressive function of p16/CDKN2 by gene transfer. The introduction of full-length p16/CDKN2 cDNA caused marked growth suppression in p16/CDKN2-null human glioma cells, but was without significant effect in those cells with endogenous wild-type p16/CDKN2 alleles. These results provide functional evidence in support of the hypothesis that the p16/CDKN2 gene is a functional growth suppressor gene, at least in gliomas.

¹ This work was supported in part by the CNPq/Brazilian National Research Council (W. A.) and by the Robert Steel Foundation for Pediatric Cancer Research (F. B. F.).

² To whom requests for reprints should be addressed, at Ludwig Institute for Cancer Research, 9500 Gilman Drive, La Jolla, CA 92093-0660.

Received 11/21/94. Accepted 1/18/95.

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