Global demethylation in loss of imprinting subtype of wilms tumor. Issue 2 (17th October 2012)

• Record Type: Journal Article
• Authors: Ludgate, Jackie L.; Le Mée, Gwenn; Fukuzawa, Ryuji; Rodger, Euan J.; Weeks, Robert J.; Reeve, Anthony E.; Morison, Ian M.
• Is Part Of: Genes, chromosomes & cancer. Volume 52:Issue 2(2013:Feb.)
• Page Start: 174
• Page End: 184
• Publication Date: 2012-10-17
• Subjects: Cancer -- Genetic aspects -- Periodicals; 616.994042
• DOI: 10.1002/gcc.22017
• Languages: English
• ISSNs: 1045-2257

Abstract

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. © 2012 Wiley Periodicals, Inc.