DELETION OF P16 AND P15 GENES IN BRAIN-TUMORS

We have used molecular genetic methods to examine the status of cell c ycle-inhibitory genes in human brain tumors. We found that p16 and a n eighboring gene, p15, were often homozygously deleted in glioblastoma multiformes but not in medulloblastomas or ependymomas, The deletions occurred in both primary tumors and their derived xenografts, but no i ntragenic mutations in either of the two genes were found. The p15 gen e was expressed in a more widespread pattern in normal tissues than gl d, but the products of both genes had similar capacities to bind to cy clin D-dependent kinases 4 and 6. These data suggest that the target o f deletion in glioblastoma multiforme includes both p15 and p16 genes. The reason that homozygous deletions, rather than intragenic mutation s, are so common in these tumors may be that deletion is a more effici ent mechanism for simultaneous inactivation of both genes.