Surprisingly, we previously observed that CpG>TpG mutations are orders of magnitude more frequent in cancer genomes from individuals with different types of postreplicative mismatch repair (MMR) deficiency or mutations in the exonuclease domain of the major leading-strand DNA polymerase ε (Pol ε), neither of which were thought to be required for the detection or repair of spontaneous deamination13. Here, EPX is linked to cancer.