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p27^Kip1: Chromosomal Mapping to 12p12–12p13.1 and Absence of Mutations in Human Tumors¹

Memorial Sloan-Kettering Cancer Center [M. V. P-C., M-H. L., E. L., K. P., L. L., S. M., J. S., J. M., C. C-C.] and Howard Hughes Medical Institute [M-H. L., J. M.], New York, New York 10021, and Albert Einstein College of Medicine, Bronx, New York 10461 [K. M., K. K.]

The p27^Kip1 gene codes for a cyclin-dependent kinase inhibitor implicated in G₁ arrest by transforming growth factor ß, cell-cell contact, agents that elevate cyclic AMP, and the growth-inhibitory drug rapamycin. p27 binds to and inhibits complexes formed by cyclin E-cdk2, cyclin A-cdk2, and cyclin D-cdk4. The involvement of p27 in the negative regulation of cell proliferation suggests that it may also function as a tumor suppressor gene. Using a combination of somatic cell hybrid panels and fluorescence in situ hybridization p27^Kip1 has been mapped to the short arm of chromosome 12 at the 12p12–12p13.1 boundary, reported to harbor deletions and rearrangements in leukemia and mesotheliomas. In order to assess potential p27^Kip1 gene alterations, we have screened a total of 147 human primary solid tumors and found no detectable cancer-specific mutations. These results argue that the often observed loss of antimitogenic transforming growth factor ß responsiveness in human cancer cells is not due to structural defects in p27^Kip1.

¹ This research was supported in part by NIH Grants CA-47538, CA-47179, CA-58514, and CA-DK-47650 (C. C-C.). J. M. is a Howard Hughes Medical Institute Investigator, and support for this work was provided in part by the Howard Hughes Medical Institute.

² To whom requests for reprints should be addressed, at Department of Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021.

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

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