DELETIONS OF THE CYCLIN-DEPENDENT KINASE-4 INHIBITOR GENE IN MULTIPLEHUMAN CANCERS

CYTOGENETIC abnormalities of chromosome 9p21 are characteristic of mal ignant melanomas(1,2), gliomas(3), lung cancers(4) and leukaemias(5). From a panel of 46 human malignant cell lines, we localized by positio nal cloning the most frequently deleted region on 9p21. Sequence analy sis of the isolated fragment reveals two open reading frames identical to the recently described complementary DNA for the inhibitor of cycl in-dependent kinase 4 (CDK4)(6). Polymerase chain reaction and Souther n blot analysis confirmed the frequent deletion or rearrangement of th e CDK4-inhibitor gene in melanomas, gliomas, lung cancers and leukaemi as, and the absence of detectable gene transcripts. One carcinoma had a deletion entirety within the CDK4-inhibitor gene. The CDK4-inhibitor gene from a patient with dysplastic nevus syndrome had a germ-line no nsense mutation. The CDK4 inhibitor is thought to be a physiological s uppressor of proliferation. Cells unable to produce the inhibitor may be prone to neoplastic transformation.