Global demethylation in loss of imprinting subtype of Wilms tumor.

Abstract

Epigenetic abnormalities at the IGF2/H19 locus play a key role in the onset of Wilms tumor. These tumors can be classified into three molecular subtypes depending on the events occurring at this locus: loss of imprinting (LOI), loss of heterozygosity (LOH), or retention of imprinting (ROI). As IGF2 LOI is a consequence of aberrant methylation, we hypothesized that this subtype of Wilms tumors might display global abnormalities of methylation. We therefore analyzed the methylation status of satellite DNA, as a surrogate for global methylation in 50 Wilms tumor patients. Satellite methylation was quantified by a methylation-sensitive quantitative PCR. We confirmed hypomethylation of both satellite α (Sat α) and satellite 2 (Sat 2) DNA in Wilms tumor samples compared with normal kidney. In addition, we found that LOI tumors, unlike ROI or LOH ones, showed concordant hypomethylation of both Sat α and Sat 2 DNA. This would suggest that the LOI subtype of Wilms tumor, which unlike other subtypes results from an epimutation, has a global deregulation of methylation mechanisms.

• Authors: Jackie L Ludgate, Gwenn Le Mée, Ryuji Fukuzawa, Euan J Rodger, Robert J Weeks, Anthony E Reeve, Ian M Morison
• Journal: Genes, chromosomes & cancer (Genes Chromosomes Cancer) Vol. 52 Issue 2 Pg. 174-84 (Feb 2013) ISSN: 1098-2264 [Electronic] United States
• PMID: 23074036 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Wiley Periodicals, Inc.

Chemical References

• DNA, Satellite
• Insulin-Like Growth Factor II

Topics

• Blotting, Southern
• DNA Methylation
• DNA, Satellite (genetics)
• Genomic Imprinting
• Genomic Instability
• Humans
• Insulin-Like Growth Factor II (genetics)
• Polymerase Chain Reaction
• Wilms Tumor (classification, genetics)