title: Loss of imprinting of insulin-like growth factor-II in Wilms' tumor commonly involves altered methylation but not mutations of CTCF or its binding site.
abstract: Loss of imprinting (LOI) is the most common molecular abnormality in Wilms' tumor (WT), other embryonal cancers, and most other tumor types. LOI in WT involves activation of the normally silent maternal allele of the insulin-like growth factor-II (IGF2) gene, silencing of the normally active maternal allele of the H19 gene, and aberrant methylation of a differentially methylated region (DMR) upstream of the maternal copy of H19. Recently, the transcription factor CTCF, which binds to the H19 DMR, has been implicated in the maintenance of H19 and IGF2 imprinting. Here, we show that mutations in the CTCF gene or in the H19 DMR do not occur at significant frequency in WT, nor is there transcriptional silencing of CTCF. We also confirm that methylation of the H19 DMR in WT with LOI includes the CTCF core consensus site. However, some WTs with normal imprinting of IGF2 also show aberrant methylation of CTCF binding sites, indicating that methylation of these sites is necessary but not sufficient for LOI in WT.
authors: Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors: H
authors: H
authors: Cui
authors: E L
authors: EL
authors: Niemitz
authors: J D
authors: JD
authors: Ravenel
authors: P
authors: P
authors: Onyango
authors: S A
authors: SA
authors: Brandenburg
authors: V V
authors: VV
authors: Lobanenkov
authors: A P
authors: AP
authors: Feinberg
mesh_terms: D000483:Alleles; D001483:Base Sequence; D001665:Binding Sites; D000076246:CCCTC-Binding Factor; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D018392:Genomic Imprinting; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D009154:Mutation; D062085:RNA, Long Noncoding; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D009396:Wilms Tumor / Q000235:genetics*
chemical_list: D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; D004268:DNA-Binding Proteins; C094335:H19 long non-coding RNA; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D022661:RNA, Untranslated; D012097:Repressor Proteins; D014157:Transcription Factors; D007335:Insulin-Like Growth Factor II