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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.

proceedings of the national academy of sciences of the united states of america

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

Loss of imprinting of the insulin-like growth factor II gene occurs by biallelic methylation in a core region of H19 -associated CTCF-binding sites in colorectal cancer