“…(2) C>T transitions at methylated cytosine in CG base pairs display a higher frequency than expected (Alexandrov et al, 2013a;Alexandrov et al, 2013b;Burgess, 2019;Hutchinson, 2013;Petljak et al, 2019). Therefore, activation-induced cytidine deaminase (AID) (Barlow et al, 2013;Greaves, 2018;Petersen-Mahrt et al, 2002) and apolipoprotein B mRNA editing enzyme catalytic (APOBEC) family (Alexandrov et al, 2013b;Buisson et al, 2019;Hutchinson, 2013;McGranahan et al, 2017;Robertson et al, 2017) catalyzing the deamination of C were identified as ESMs. Unfortunately, some cancers such as kidney renal clear cell carcinoma (KIRC) show the low mutation proportion at CG base pairs and low APOBEC expression (Burns et al, 2013b), raising the potential roles of unidentified ESMs.…”