Reduced expression of the cyclin-dependent kinase inhibitor gene p57(KIP2) in Wilms' tumor

Jeffrey S. Thompson, Kimberly J. Reese, Michael R. DeBaun, Elizabeth J. Perlman, Andrew P. Feinberg*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

75 Scopus citations

Abstract

We have previously shown that the p57(KIP2) gene, which encodes a cyclin-dependent kinase inhibitor, undergoes genomic imprinting and lies within a 700-kb domain of imprinted genes on 11p15, including IGF2 and H19. Loss of heterozygosity and loss of imprinting (LOI) of this region are frequently observed in Wilms' tumor (WT) and other embryonal malignancies. Although LOI of p57(KIP2) was observed in some WTs (~10%), allele-specific expression was preserved in most tumors examined. Because our initial studies were inconclusive concerning the absolute expression level of p57(KIP2) in WT, we developed a sensitive and quantitative RNase protection assay to determine if changes in p57(KIP2) expression play a role in WT. Expression of p57(KIP2) was found to be virtually absent in 21 of 21 WTs compared to matched normal kidney from the same patients, as well as compared to fetal kidney. We also examined p57(KIP2) expression in the normal kidney and tongue of patients with Beckwith-Wiedemann syndrome (BWS), which predisposes to WT and also involves LOI of IGF2 and H19. Although p57(KIP2) was undetectable in BWS tongue, similar results were also observed in postnatal non-BWS tongue samples. Most primary skin fibroblast cultures of BWS cell lines exhibited normal imprinting of p57(KIP2). However, one BWS patient did show LOI of p57(KIP2) in skin fibroblasts. Thus, p57(KIP2) is part of a domain of genes on 11p15 that show altered expression and, in some cases, altered imprinting in WT and BWS.

Original languageEnglish (US)
Pages (from-to)5723-5727
Number of pages5
JournalCancer Research
Volume56
Issue number24
StatePublished - Dec 15 1996

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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