MLH1 and colorectal cancer: Some of the best described “classical” high penetrance genes include BRCA1/2, for which germline mutations are associated with an elevated risk of ovarian and breast cancer [6], MLH1/MSH2 linked to colorectal cancer [7], CDKN2A and RB1, associated with melanoma and retinoblastoma, respectively [8–10], as well as TP53, associated with the Li-Fraumeni syndrome with an elevated risk for multiple cancer forms [11].