Open AccessAPOBEC3A catalyzes mutation and drives carcinogenesis in vivo
Author(s) -
Emily K. Law,
Rena LevinKlein,
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 Isaksson Vogel,
Spyridon Stavrou,
Alexya N. Aguilera,
Sandra Wagner,
David A. Largaespada,
Timothy K. Starr,
Susan R. Ross,
Reuben S. Harris
Publication year - 2020
Publication title -
the journal of experimental medicine/the journal of experimental medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.483
H-Index - 448
eISSN - 1540-9538
pISSN - 0022-1007
DOI - 10.1084/jem.20200261
Subject(s) - apobec , carcinogenesis , mutagenesis , biology , mutation , cytosine deaminase , genetics , cancer research , dna damage , dna , microbiology and biotechnology , cancer , gene , genome , genetic enhancement
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.