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p57 KIP2 is expressed in Wilms' tumor with LOH of IIp15.5
Author(s) -
Overall Maree L.,
Spencer James,
Bakker Marilyn,
Dziadek Marie,
Smith Peter J.
Publication year - 1996
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/(sici)1098-2264(199609)17:1<56::aid-gcc8>3.0.co;2-1
Subject(s) - loss of heterozygosity , wilms' tumor , biology , gene , microbiology and biotechnology , allele , tumor suppressor gene , cancer research , genomic imprinting , gene expression , genetics , carcinogenesis , dna methylation
Abstract p57 KIP2 is a cyclin‐dependent kinase inhibitor that maps to human chromosome band IIp15.5, placing it in a genomicaly imprinted region that has been implicated in the etiology of Wilms' tumor and in the Beckwith‐Wiedemann syndrome. Recent analysis of p57 KIP2 expression in the mouse has determined that this gene is exclusively expressed from the maternal allele. It has been suggested that p57 KIP2 is the WT2 tumor suppressor gene in the IIp15.5 region. We have used reverse transcriptase‐PCR to determine whether loss of p57 KIP2 expression occurs in Wilms' tumor samples that have undergone maternal loss of heterozygosity of IIp15.5. p57 KIP2 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 p57 KIP2 expression in tumor tissue is not markedly different from that in normal kidney. Our data indicate that if the p57 KIP2 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 p57 KIP2 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 p57 KIP2 may not be the WT2 gene. Genes Chromosom Cancer 17:56–59 (1996) . © 1996 Wiley‐Liss, Inc.