MOLECULAR-CLONING AND CHROMOSOMAL LOCALIZATION OF THE HUMAN CYCLIN-C (CCNC) AND CYCLIN-E (CCNE) GENES - DELETION OF THE CCNC GENE IN HUMAN TUMORS

The human G1-phase cyclins are important regulators of cell cycle prog ression that interact with various cyclin-dependent kinases and facili tate entry into S-phase. We have confirmed the localization of the hum an cyclin C (CCNC) gene to chromosome 6q21 and of human cyclin E (CCNE ) to 19q12. The CCNC gene structure was also determined, and we have s hown that it is deleted in a subset of acute lymphoblastic leukemias, including a patient sample containing a t(2;6)(p21;q15), with no appar ent cytogenetic deletion. Single-strand conformational polymorphism an alysis of the remaining CCNC allele from patients with a deletion of o ne allele established that there were no further mutations within the exons or the flanking intronic sequences. These results suggest either that haploinsufficiency of the cyclin C protein is sufficient to prom ote tumorigenesis or that the important tumor suppressor gene is linke d to the CCNC locus. (C) 1996 Academic Press, Inc.