Prospectively defined patterns of APOBEC3A mutagenesis are prevalent in human cancers

Rachel A. DeWeerd, Eszter Németh, Ádám Póti, Nataliya Petryk, Chun Long Chen, Olivier Hyrien, Dávid Szüts, Abby M. Green

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Mutational signatures defined by single base substitution (SBS) patterns in cancer have elucidated potential mutagenic processes that contribute to malignancy. Two prevalent mutational patterns in human cancers are attributed to the APOBEC3 cytidine deaminase enzymes. Among the seven human APOBEC3 proteins, APOBEC3A is a potent deaminase and proposed driver of cancer mutagenesis. In this study, we prospectively examine genome-wide aberrations by expressing human APOBEC3A in avian DT40 cells. From whole-genome sequencing, we detect hundreds to thousands of base substitutions per genome. The APOBEC3A signature includes widespread cytidine mutations and a unique insertion-deletion (indel) signature consisting largely of cytidine deletions. This multi-dimensional APOBEC3A signature is prevalent in human cancer genomes. Our data further reveal replication-associated mutations, the rate of stem-loop and clustered mutations, and deamination of methylated cytidines. This comprehensive signature of APOBEC3A mutagenesis is a tool for future studies and a potential biomarker for APOBEC3 activity in cancer.

Original languageEnglish
Article number110555
JournalCell Reports
Volume38
Issue number12
DOIs
StatePublished - Mar 22 2022

Keywords

  • APOBEC3
  • CP:Cancer
  • cancer genome
  • cytidine deaminase
  • indel
  • methylcytidine
  • mutagenesis
  • mutational signature

Fingerprint

Dive into the research topics of 'Prospectively defined patterns of APOBEC3A mutagenesis are prevalent in human cancers'. Together they form a unique fingerprint.

Cite this