The cause of IGF2 LOI in CRC might not be an alteration of DNA methylation within the IGF2/H19 domain, but rather the dysfunction of any of the components related to imprinting regulation, such as the intrachromosomal loop, sequence alteration of H19-DMR, or expression of the CTCF or PRC2 complexes [41]. The gene discussed is IGF2; the disease is colorectal carcinoma.