While methylation is restricted to the shared MLH1-EMP2AIP1 CpG island in carriers of a CME, multiple genes flanking MLH1 in a 50 kb region are concomitantly hypermethylated in sporadic MSI, MLH1-hypermethylated CRC, leading to regional transcriptional silencing in these tumours [10, 31]. This evidence concerns the gene MLH1 and colorectal carcinoma.