However, in the case of frequent and widespread methylation events in CIMP tumors, very few clearly established “driver” hypermethylation events of tumorigenesis (which we define as epigenetic silencing of active genes leading to cancer initiation and progression) are documented—the most common being hypermethylation of MLH1 in CRCs, which rapidly increases the rate of malignancy [79]. Here, MLH1 is linked to cancer.