p57(KIP2) is not mutated in hepatoblastoma but shows increased transcriptional activity in a comparative analysis of the three imprinted genes p57(KIP2), IGF2, and H19

Hepatoblastomas (HBs), representing malignant liver tumors of childhood, sh ow frequent loss of heterozygosity (LOH) in the chromosomal region. 11p15.5 , This loss is of maternal origin suggesting the presence of a monoallelica lly expressed tumor suppressor gene in this region. p57(KIP2) (KIP2) locate d at 11p15.5 is predominantly expressed from the maternal allele and encode s a cyclin-dependent kinase inhibitor. We screened a series of 56 HE tumors and five HE cell lines for allelic loss (LOH) of the KIP2 locus by microsa tellite analysis and KIP2 coding sequence mutations by single-strand confor mation polymorphism analysis. Although LOH at the KIP2 locus occurred in 25 % of the cases, no mutations were found. Analysis of KIP2 mRNA expression b y competitive reverse transcriptase-polymerase chain reaction revealed up-r egulation in nine of 12 HBs compared to matching Liver samples. In contrast , mRNA levels of the putative suppressor gene H19 on 11p15.5 were decreased in 10 of 12 tumors, indicating that KIP2 and H19 are not co-regulated in H Bs, IGF2 mRNA expression was increased in 11 of 12 HE samples. All HBs show ed monoallelic KIP2 expression However, the overexpression of KIP2 in HBs w ith maternal loss of 11p15.5 suggests a reactivation of the paternal allele in these cases. Overexpression of KIP2 in HBs argues against a role as a H E suppressor gene.