PMS2 and colorectal carcinoma: However, it has been shown that methylation of MMR genes (such as MLH1, MSH2, MSH6 and PMS2) is an underlying mechanism of sporadic MSI-H CRC, and methylation status in combination with MSI could therefore be useful in discriminating sporadic from LS-associated CRC (Young et al, 2001; Hitchins et al, 2007).