P27(KIP1) - CHROMOSOMAL MAPPING TO 12P12-12P13.1 AND ABSENCE OF MUTATIONS IN HUMAN TUMORS

The p27(Kip1) gene codes for a cyclin-dependent kinase inhibitor impli cated in G(1) arrest by transforming growth factor beta, cell-cell con tact, agents that elevate cyclic AMP, and the growth-inhibitory drug r apamycin. p27 binds to and inhibits complexes formed by cyclin E-cdk2. cyclin A-cdk2, and cyclin D-cdk4. The involvement of p27 in the negat ive regulation of cell proliferation suggests that it may also functio n as a tumor suppressor gene. Using a combination of somatic cell hybr id panels and fluorescence in situ hybridization p27(Kip1) has been ma pped to the short arm of chromosome 12 at the 12p12-12p13.1 boundary, reported to harbor deletions and rearrangements in leukemia and mesoth eliomas. Zn order to assess potential p27(Kip1) gene alterations, we h ave screened a total of 147 human primary solid tumors and found no de tectable cancer-specific mutations. These results argue that the often observed loss of antimitogenic transforming growth factor beta respon siveness in human cancer cells is not due to structural defects in p27 (Kip1).