Eight MSI-H cancers and one pathogenic POLE mutation (V411L) were identified, which made up 30% of all hypermutated tumours and had a significantly higher TMB compared to the other samples; median 42.5 (34.0–56.5) versus 5.1 (3.9–7.2) mutations/Mb (p < 0.001), respectively. Here, POLE is linked to cancer.