Genomic imprinting of human p57(KIP2) and its reduced expression in Wilms' tumors

p57(KIP2) is a potent tight-binding inhibitor of several G(1) cyclin complexes, and is a negative regulator of cell proliferation. The gene encoding human p57(KIP2) is located on chromosome 11p15.5, a region implicated in both sporadic cancers and Beckwith-Wiedemann syndrome (BWS), a cancer syndrome, making it a tumor suppressor candidate. Several types of childhood tumors including Wilms' tumor, adrenocortical carcinoma and rhabdomyosarcoma display a specific loss of maternal 11p15 alleles, suggesting that genomic imprinting plays an important part. Genetic analysis of the familial BWS has indicated maternal carriers and suggested a role in genomic imprinting. Previously, we demonstrated that p57(KIP2) is imprinted in the mouse. Here we describe the genomic imprinting of human p57(KIP2) and the reduction of its expression in Wilms' tumors. High resolution mapping locates p57(KIP2) in the region responsible for both tumor suppressivity and BWS.