Furthermore, unsupervised hierarchical clustering of SBS mutational signature profiles revealed clusters characterized by signatures such as SBS7a/b (UV damage), SBS2 and SBS13 (APOBEC activity), SBS6, SBS14, SBS15, SBS20, and SBS21 (MMR deficiency), and SBS10a/b (POLE deficiency),67,68,69,70,71 which suggest that somatic MCM8/MCM9 variants may be secondary to other DNA repair deficiencies and mutational processes (Figure S7). This evidence concerns the gene MCM9 and mismatch repair cancer syndrome 1.