Global demethylation in loss of imprinting subtype of Wilms tumor.
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.
Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
Jackie L
JL
Ludgate
Gwenn
G
Le Mée
Ryuji
R
Fukuzawa
Euan J
EJ
Rodger
Robert J
RJ
Weeks
Anthony E
AE
Reeve
Ian M
IM
Morison
D015139:Blotting, Southern; D019175:DNA Methylation; D004276:DNA, Satellite / Q000235:genetics*; D018392:Genomic Imprinting; D042822:Genomic Instability; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D016133:Polymerase Chain Reaction; D009396:Wilms Tumor / Q000145:classification / Q000235:genetics*
D004276:DNA, Satellite; D007335:Insulin-Like Growth Factor II