POLE and cancer: Analogous to CRC, patients with endometrial cancers harbouring pathogenic POLE exonuclease domain mutations have excellent prognosis [6, 7, 10, 12], possibly because such an extreme hypermutation event causes the enrichment of antigenic neoepitopes, which in turn stimulates a potent cytotoxic T-cell response in cancer cells [9, 13, 14].