2008
DOI: 10.1093/hmg/ddn163
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Somatically acquired hypomethylation of IGF2 in breast and colorectal cancer

Abstract: The imprinted insulin-like growth factor 2 (IGF2) gene is expressed predominantly from the paternal allele. Loss of imprinting (LOI) associated with hypomethylation at the promoter proximal sequence (DMR0) of the IGF2 gene was proposed as a predisposing constitutive risk biomarker for colorectal cancer. We used pyrosequencing to assess whether IGF2 DMR0 methylation is either present constitutively prior to cancer or whether it is acquired tissue-specifically after the onset of cancer. DNA samples from tumour t… Show more

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Cited by 119 publications
(127 citation statements)
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“…Previous studies investigating peripheral blood methylation variability in relation to cancer risk have focused mainly on rare epimutations or genome-wide methylation levels (25,39). Only a few studies have investigated gene-specific DMRs and all of these have been carried out in small retrospective studies or used nonquantitative methods (26)(27)(28)(29).…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…Previous studies investigating peripheral blood methylation variability in relation to cancer risk have focused mainly on rare epimutations or genome-wide methylation levels (25,39). Only a few studies have investigated gene-specific DMRs and all of these have been carried out in small retrospective studies or used nonquantitative methods (26)(27)(28)(29).…”
Section: Discussionmentioning
confidence: 99%
“…Previous reports of WBC DNA methylation and cancer risk include studies of global DNA methylation levels in repeat regions across the genome (e.g., LINE1, Alu) or 5-mC content in genomic DNA (16)(17)(18)(19)(20); studies of genespecific DNA methylation levels in candidate genes (14,(21)(22)(23)(24)(25)(26)(27)(28)(29), and genome-wide DNA methylation microarray studies (15,(30)(31)(32). Although these studies provide enticing findings, most included relatively small study populations and/or used samples collected after diagnosis, thus raising concerns about reverse causality and the potential confounding influences of active disease or treatment on DNA methylation in blood (25). Most research on DNA methylation in cancer has focused on gene promoter CpG islands (CGI).…”
Section: Introductionmentioning
confidence: 99%
“…One study indicates that IGF2 DMR0 hypo-methylation occurs as an acquired tissue-specific somatic event, rather than a constitutive innate epimutation in tumor tissues. 40 It should be important to further explore the mechanisms that regulate the imprinting of the IGF2/H19 in the NTDs.…”
Section: Discussionmentioning
confidence: 99%
“…The CG genes SOHLH2, SSX2, SSX4B, SSX8, SSX9, and PAGE5 are also recurrently hypomethylated in GBM (Wu et al 2010). Promoter hypomethylation is associated with transcriptional activation at other single-copy genes, for example IGF2/H19 (associated with loss of imprinting) (Cui et al 2002;Ito et al 2008), CA9 (Cho et al 2001), and SRPX2 (Oster et al 2013). As ;98% of 59 promoter CpG islands (CGIs) are unmethylated in brain (Maunakea et al 2010), they are more frequently targets of aberrant hypermethylation in cancer (Costello et al 2000;Zardo et al 2002).…”
mentioning
confidence: 99%