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Genes Chromosomes Cancer. 1996 Sep;17(1):56-9.

p57K1P2 is expressed in Wilms' tumor with LOH of 11p15.5.

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1
Department of Anatomy and Cell Biology, University of Melbourne, VIC Australia.

Abstract

p57KIP2 is a cyclin-dependent kinase inhibitor that maps to human chromosome band 11p15.5, placing it in a genomically imprinted region that has been implicated in the etiology of Wilms' tumor and in the Beckwith-Wiedemann syndrome. Recent analysis of p57KIP2 expression in the mouse has determined that this gene is exclusively expressed from the maternal allele. It has been suggested that p57KIP2 is the WT2 tumor suppressor gene in the 11p15.5 region. We have used reverse transcriptase PCR to determine whether loss of p57KIP2 expression occurs in Wilms' tumor samples that have undergone maternal loss of heterozygosity of 11p15.5. p57KIP2 mRNA was amplified in both the Wilms' tumor tissue and in normal kidney tissue of all five patients analyzed. Semi-quantitative PCR analyses demonstrated that the relative level of p57KIP2 expression in tumor tissue is not markedly different from that in normal kidney. Our data indicate that if the p57KIP2 gene is imprinted in humans and expressed exclusively from the maternal allele, reactivation of the paternal allele has occurred in all five Wilms' tumor samples analyzed in this study. Sequence analysis of the p57KIP2 Cdk inhibitory domain in genomic DNA from primary and secondary tumors from two patients showed only a single base change in one secondary WT, resulting in a predicted methionine to isoleucine substitution at amino acid position 70. These studies suggest that p57KIP2 may not be the WT2 gene.

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