P57(KIP2) IS EXPRESSED IN WILMS-TUMOR WITH LOH OF 11P15.5

p57(K1P2) is a cyclin-dependent kinase inhibitor that maps to human ch romosome band 11p15.5, placing it in a genomically imprinted region th at has been implicated in the etiology of Wilms' tumor and in the Beck with-Wiedemann syndrome, Recent analysis of p57(K1P2) expression in th e mouse has determined that this gene is exclusively expressed from th e maternal allele. It has been suggested that p57(K1P2) is the WT2 tum or suppressor gene in the 11p15.5 region. We have used reverse transcr iptase-PCR to determine whether loss of p57(K1P2) expression occurs in Wilms' tumor samples that have undergone maternal loss of heterozygos ity of 11p 15.5. p57(K1P2) mRNA was amplified in both the Wilms' tumor tissue and in normal kidney tissue of all five patients analyzed. Sem i-quantitative PCR analyses demonstrated that the relative level of p5 7(K1P2) expression in tumor tissue is not markedly different from that in normal kidney. Our data indicate that if the p57(K1P2) gene is imp rinted in humans and expressed exclusively from the maternal allele, r eactivation of the paternal allele has occurred in all five Wilms' tum or samples analyzed in this study. Sequence analysis of the p57(K1P2) Cdk inhibitory domain in genomic DNA from primary and secondary tumors from two patients showed only a single base change in one secondary W T, resulting in a predicted methionine to isoleucine substitution at a mino acid position 70. These studies suggest that p57(K1P2) may not be the WT2 gene. (C) 1996 Wiley-Liss, Inc.