REPLACEMENT OF THE P16 CDKN2 GENE SUPPRESSES HUMAN GLIOMA CELL-GROWTH/

The p16/CDKN2 gene has many features of a growth suppressor gene: it m aps 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. How ever, the lower frequency of alteration of the gene in primary tumor t issue as compared to the cognate tumor cell lines has brought this int erpretation into question. We have assessed the growth suppressive fun ction of p16/CDKN2 by gene transfer. The introduction of full-length p 16/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 function al evidence in support of the hypothesis that p16/CDKN2 gene is a func tional growth suppressor gene, at least in gliomas.