Defects in different DNA repair pathways are associated with distinct somatic mutation profiles. For example, SNVs and indels can arise from errors during base excision repair, nucleotide excision repair, and transcription-coupled repair (33). Moreover, the action of the apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like-3 (APOBEC3) family of cytosine deaminase proteins can lead to cytidine-to-uridine transition mutations on single-strand DNA that, upon replication, lead to guanosine-to-adenosine mutations on the opposing DNA strand (34). Errors made during DNA mismatch repair also can lead to either interspersed SNVs or indels within microsatellite repeat sequences, whereas errors made during double-strand break repair by homologous recombination, NHEJ, or alternative-NHEJ can lead to CNVs (35, 36).
