Mechanisms of APOBEC3 mutagenesis in human cancer cells

Abstract The APOBEC3 family of cytosine deaminases has been implicated in some of the most prevalent mutational signatures in cancer 1–3 . However, a causal link between endogenous APOBEC3 enzymes and mutational signatures in human cancer genomes has not been established, leaving the mechanisms of APOBEC3 mutagenesis poorly understood. Here, to investigate the mechanisms of APOBEC3 mutagenesis, we deleted implicated genes from human cancer cell lines that naturally generate APOBEC3-associated mutational signatures over time 4 . Analysis of non-clustered and clustered signatures across whole-genome sequences from 251 breast, bladder and lymphoma cancer cell line clones revealed that APOBEC3A deletion diminished…

• PC
  Pew Charitable Trusts
• VF
  V Foundation for Cancer Research

  Award: P30 CA008748
• EM
  European Molecular Biology Organization
• MS
  Memorial Sloan-Kettering Cancer Center

  Award: CA008748
• EF
  Emerald Foundation
• CR
  Cancer Research UK

  Award: C98/A24032
• MR
  Medical Research Council

  Awards: U105178808, C98/A24032
• NC
  National Cancer Institute

  Awards: R00CA212290, R37CA261183, CA008748, P30 CA008748, R01ES030993, R01ES030993-01A1