Hypermethylation of MLH1 is primarily considered to be the hallmark of non-familial MSI-H tumors, while mutations in MLH1,MSH2, MSH6 and to a lesser extent, PMS1, are known to drive Lynch syndrome, an inherited condition that increases the risk primarily for MSI-H-related CRC [23]. The gene discussed is MSH6; the disease is colorectal carcinoma.