Abstract

We hypothesize that loss of imprinting (LOI) of the insulin-like growth factor II ( IGF2 ) gene is associated with a predisposition to sporadic colorectal cancer. We confirmed a previously known strong correlation between LOI and microsatellite instability and showed that LOI was not a consequence of microsatellite instability or mismatch repair deficiency. LOI of IGF2 correlated strongly with biallelic hypermethylation of a core of five CpG sites in the insulator region of IGF2/H19 , which is a known CTCF-binding element. As this methylation-dependent LOI was present in both tumors and normal colonic mucosa, it is possible that hypermethylation creates a field defect predisposing to cancer.

Keywords

Microsatellite instabilityImprinting (psychology)CTCFDNA methylationBiologyCpG siteGenomic imprintingCancer researchInsulin-like growth factor 2MethylationColorectal cancerDNA mismatch repairMolecular biologyCancerGeneticsGeneTranscription factorMicrosatelliteAlleleGene expressionEnhancer

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Year
2000
Type
article
Volume
98
Issue
2
Pages
591-596
Citations
227
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Hidewaki Nakagawa, Robert B. Chadwick, Païvi Peltomäki et al. (2000). Loss of imprinting of the insulin-like growth factor II gene occurs by biallelic methylation in a core region of <i>H19</i> -associated CTCF-binding sites in colorectal cancer. Proceedings of the National Academy of Sciences , 98 (2) , 591-596. https://doi.org/10.1073/pnas.98.2.591

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DOI
10.1073/pnas.98.2.591