APOBEC-induced mutations in human cancers are strongly enriched on the lagging DNA strand during replication

Properties of cancers associated with the APOBEC mutational signature (r_apo). (A,B) Correlation between r_apo and the number of kataegistic mutations +0.5 per tumor in WGS (A) and WES (B) data sets. (C) Correlation of r_apo and the level of expression of APOBEC3B per tumor in the WES data set. (D) Box plots representing r_apo per tumor type; WES data set: (ACC) adrenocortical carcinoma; (BLCA) bladder cancer; (BRCA) breast cancer; (CESC) cervical squamous cell carcinoma; (ESCA) esophageal carcinoma; (HNSC) head and neck squamous cell carcinoma; (LUAD) lung adenocarcinoma; (LUSC) lung squamous cell carcinoma; (READ) rectum adenocarcinoma; (SKCM) cutaneous melanoma. (E) Distributions of r_apo in WGS and WES data sets. Tumors with r_apo < 1 were categorized as APOpoor, and tumors with r_apo > 5, as APOrich. (F) Enrichment of dispersed and clustered APOBEC signature mutations in the proximity of rearrangement breakpoints (used as a proxy for DSBs) in the WGS data set. The observed mutation rates in the proximity (up to 100 kb) of rearrangement breakpoints were compared with the average mutation rates per tumor in APOrich tumors.