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Deletion of p16 and p15 Genes in Brain Tumors¹

The Johns Hopkins Oncology Center, Baltimore, Maryland 21231 [J. J., N. P., K. W. K., B. V.]; the Verna and Marrs McLean Department of Biochemistry, Baylor College of Medicine, Houston, Texas 77030 [J. W. H.]; the Department of Pathology, Duke University School of Medicine, Durham, North Carolina 27710 [S. H. B., D. D. B.]; and the Department of Medicine and Ireland Cancer Center, University Hospital of Cleveland and Case Western Reserve University, Cleveland, Ohio 44106 [S. M., J. K. V. W.]

We have used molecular genetic methods to examine the status of cell cycle-inhibitory genes in human brain tumors. We found that p16 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 p15 gene was expressed in a more widespread pattern in normal tissues than p16, 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 p15 and p16 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.

¹ This work was supported by the Preuss Foundation; the Clayton Fund; the National Foundation for Cancer Research; Baylor SPORE in Prostate Cancer; NIH Grants CA-58204 (J. W. H.), AG-11085 (S. J. E., J. W. H.), CA-43733 and CA-51504 (S. H. B.), CA-11898 and NS-20023 (D. D. B.), CA-57208 (S. M.), CA-51183 (J. W.), CA-41183 (B. V.), and CA-09243 (J. J.). B. V. is an American Cancer Society Research Professor.

² To whom requests for reprints should be addressed.

Received 10/11/94. Accepted 11/ 3/94.

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