Premium
Global demethylation in loss of imprinting subtype of wilms tumor
Author(s) -
Ludgate Jackie L.,
Le Mée Gwenn,
Fukuzawa Ryuji,
Rodger Euan J.,
Weeks Robert J.,
Reeve Anthony E.,
Morison Ian M.
Publication year - 2013
Publication title -
genes, chromosomes and cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.754
H-Index - 119
eISSN - 1098-2264
pISSN - 1045-2257
DOI - 10.1002/gcc.22017
Subject(s) - wilms' tumor , methylation , imprinting (psychology) , dna methylation , epigenetics , loss of heterozygosity , biology , genomic imprinting , cancer research , locus (genetics) , microbiology and biotechnology , genetics , dna , gene , gene expression , allele
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.