POLE EDM in combination with MMR loss causes a distinct mutational signature in EC (COSMIC signature 14) 1, 38 – the observation that this is not universal in cases with both defects supports the notion that these tumours are a heterogeneous group, where MSI/MMRd could be acquired after POLE EDM and vice versa, with differing impacts on prognosis. This evidence concerns the gene POLE and neoplasm.