In 25% (4/16) of CHEK2-deficient cancers, tissue-specific signatures, including mutational signature SBS15 (defective DNA-mismatch repair) in two CRCs (1 with somatic MSH2 inactivation) and mutational signatures SBS2 and SBS13 (APOBEC-related signatures) in 2 breast cancers, were identified (Figure 1, D). The gene discussed is CHEK2; the disease is breast cancer.