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Assignment of the Human p27^Kip1 Gene to 12p13 and Its Analysis in Leukemias¹

The Johns Hopkins Oncology Center, Baltimore, Maryland 21231 [J. A. P., N. P., B. L., K. W. K., B. V.]; Fred Hutchinson Cancer Research Center, Seattle, Washington 98104 [J. M. R.]; Department of Molecular Biotechnology, University of Washington School of Medicine, Seattle, Washington 98195 [C. F., B. T.]; and Department of Medicine, The University of Chicago, Chicago, Illinois 60637 [S. K. B., S. Y., J. D. R.]

The p27^Kip1 (p27) gene encodes an inducible inhibitor of cyclin-dependent kinase activity. Using a murine p27 cDNA as probe, we obtained a human cDNA clone and subsequently used it to isolate a genomic clone of this gene. The coding region of the human p27 gene was contained in two exons. Both the amino acid sequence and intron-exon organization of p27 were similar to those previously found for the related cyclin-dependent kinase inhibitor p21^Waf1 (p21). The p27 gene was localized to chromosome band 12p13 by a combination of somatic cell hybrid and fluorescence in situ hybridization analyses. The p27 gene product is thought to control the leukocyte cell cycle and the 12p13 chromosomal band is known to be deleted in leukemias, suggesting that the p27 gene may act as a tumor suppressor gene in leukemias. Although p27 was found to reside in the minimal region of chromosomal loss in hematological malignancies, no mutations of p27 were observed in leukemia samples. Haploinsufficiency of p27 may confer a growth advantage to leukemia cells.

¹ This research was supported in part by NIH Grants CA 43460 (B. V.) and CA42577 (J. D. R.), Department of Energy Grants DE-FGO2-86ER60408 (J. D. R.) and DE-FG06-93ER61553 (B. T.), and the Pruess Foundation. B. V. is an American Cancer Society Research Professor.

² To whom requests for reprints should be addressed, at the Johns Hopkins Oncology Center, Molecular Genetics Laboratory, 424 North Bond Street, Baltimore, MD 21231-1001.

Received 12/ 1/94. Accepted 2/10/95.

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