APOBEC3A catalyzes mutation and drives carcinogenesis in vivo

Emily K. Law, Rena Levin-Klein, Matthew C. Jarvis, Hyoung Kim, Prokopios P. Argyris, Michael A. Carpenter, Gabriel J. Starrett, Nuri A. Temiz, Lindsay K. Larson, Cameron Durfee, Michael B. Burns, Rachel I. Vogel, Spyridon Stavrou, Alexya N. Aguilera, Sandra Wagner, David A. Largaespada, Timothy K. Starr, Susan R. Ross, Reuben S. Harris

Research output: Contribution to journalArticlepeer-review

72 Scopus citations


The APOBEC3 family of antiviral DNA cytosine deaminases is implicated as the second largest source of mutation in cancer. This mutational process may be a causal driver or inconsequential passenger to the overall tumor phenotype. We show that human APOBEC3A expression in murine colon and liver tissues increases tumorigenesis. All other APOBEC3 family members, including APOBEC3B, fail to promote liver tumor formation. Tumor DNA sequences from APOBEC3A-expressing animals display hallmark APOBEC signature mutations in TCA/T motifs. Bioinformatic comparisons of the observed APOBEC3A mutation signature in murine tumors, previously reported APOBEC3A and APOBEC3B mutation signatures in yeast, and reanalyzed APOBEC mutation signatures in human tumor datasets support cause-and-effect relationships for APOBEC3A-catalyzed deamination and mutagenesis in driving multiple human cancers.

Original languageEnglish (US)
Article numbere20200261
JournalJournal of Experimental Medicine
Issue number12
StatePublished - Dec 7 2020
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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