However, tumors with mismatch repair deficiency (MMRd), tumors that show a high level of activity of the APOBEC cytidine deaminases and tumors with high Signatures 5 and 8 (both of unknown aetiology), demonstrate the most dramatic fold increase of spacer mutability compared to control sequences (Figure 2D and Supplementary Figure S8). This evidence concerns the gene CDA and mismatch repair cancer syndrome 1.