POLE and endometrial cancer: More recently, specific mutator alleles altering the exonuclease (proofreading) domain of replicative DNA polymerases δ and ε (Pol δ and Pol ε), such as POLE-P286R, were found to foster SNV hyper-mutation in the presence of functional MMR, and drive the development of hereditary colorectal or endometrial cancers (4–6).