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 incolorectal cancer

We hypothesize that loss of imprinting (LOI) of the insulin-like growth fac tor II (IGF2) gene is associated with a predisposition to sporadic colorect al cancer. We confirmed a previously known strong correlation between LOI a nd microsatellite instability and showed that LOI was not a consequence of microsatellite instability or mismatch repair deficiency. LOI of IGF2 corre lated 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 co lonic mucosa, it is possible that hypermethylation creates a field defect p redisposing to cancer.