The MMR genes hMLH1, hPMS2, and hMSH2 (and EPCAM, which secondarily targets inactivation of hMSH2) when mutated in the germline and the second allele somatically inactivated in the tumor completely inactivates DNA MMR function, generates an MSI-H cancer [30], and patients do not derive a benefit from adjuvant 5-FU therapy [17]. Here, MRC1 is linked to cancer.