Deletion of pl6 and p15 Genes in Brain Tumors

We have used molecular genetic methods to examine the status of cell cycle-inhibitory genes in human brain tumors. We found that pl6 and a neighboring 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 intragenic mutations in either of the two genes were found. The p75 gene was expressed in a more widespread pattern in normal tissues than pl6, but the products of both genes had similar capacities to bind to cyclin D-dependent kinases 4 and 6. These data suggest that the target of deletion in glioblastoma multiforme includes both pl5 and pl6 genes. The reason that homozygous deletions, rather than intragenic mutations, are so common in these tumors may be that deletion is a more efficient mechanism for simultaneous inactivation of both genes.