Loss of imprinting of insulin-like growth factor-II in Wilms' tumor commonly involves altered methylation hut not mutations of CTCF or its binding site

Loss of imprinting (LOI) is the most common molecular abnormality in Wilms' tumor (WT), other embryonal cancers, and most other tumor types. LOI in WT involves activation of the normally silent maternal allele of the insulin- like growth factor-ii (IGF2) gene, silencing of the normally active materna l allele of the H19 gene, and aberrant methylation of a differentially meth ylated region (DMR) upstream of the maternal copy of H19, Recently, the tra nscription factor CTCF, which binds to the H19 DMR, has been implicated in the maintenance of H19 and IGF2 imprinting. Here, we show that mutations in the CTCF gene or in the H19 DMR do not occur at significant frequency in W T, nor is there transcriptional silencing of CTCF, We also confirm that met hylation of the H19 DMR in WT with LOI includes the CTCF core consensus sit e. However, some WTs with normal imprinting of IGF2 also show aberrant meth ylation of CTCF binding sites, indicating that methylation of these sites i s necessary but not sufficient for LOI in WT.