Data from Frequency and Timing of Loss of Imprinting at 11p13 and 11p15 in Wilms' Tumor Development

Abstract

<div>Abstract<p>Epigenetic changes occur frequently in Wilms' tumor (WT), especially loss of imprinting (LOI) of <i>IGF2/H19</i> at 11p15. Our previous results have identified imprinted transcripts (<i>WT1-AS</i> and <i>AWT1</i>) from the <i>WT1</i> locus at 11p13 and showed LOI of these in some WTs. In this article, we set out to test the relationship between LOI at 11p13 and 11p15 and their timing in WT progression relative to other genetic changes. We found a higher level (83%) of 11p13 LOI in WT than of 11p15 LOI (71%). There was no correlation between methylation levels at the 11p13 and 11p15 differentially methylated regions or between allelic expression of <i>WT1-AS/AWT1</i> and <i>IGF2</i>. Interestingly, retention of normal imprinting at 11p13 was associated with a small group of relatively late-onset, high-stage WTs. An examination of genetic and epigenetic alterations in nephrogenic rests, which are premalignant WT precursors, showed that LOI at both 11p13 and 11p15 occurred before either 16q loss of heterozygosity (LOH) or 7p LOH. This suggests that these LOH events are very unlikely to be a cause of LOI but that LOH may act by potentiating the effects of overexpression of <i>IGF2</i> and/or <i>WT1-AS/AWT1</i> that result from LOI. (Mol Cancer Res 2008;6(7):1114–23)</p></div>