APOBEC3A catalyzes mutation and drives carcinogenesis in vivo
Abstract
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Sep 01, 2020
- Source ID
- 10.1084/jem.20200261
Entities
People
- Alexya N. Aguilera
- Cameron Durfee
- David A. Largaespada
- Emily K. Law
- Gabriel J Starrett
- Hyoung Kim
- Lindsay K. Larson
- Matthew C. Jarvis
- Michael B Burns
- Michael Carpenter
- Nuri A Temiz
- Prokopios Argyris
- Rachel Isaksson Vogel
- Rena Levin-Klein
- Reuben S Harris
- Sandra Wagner
- Spyridon Stavrou
- Susan R. Ross
- Timothy K Starr
Organizations
- Howard Hughes Medical Institute
- Loyola University Chicago
- National Cancer Institute
- National Institute of Allergy and Infectious Diseases
- National Institute on Aging
- National Institutes of Health
- The Cancer Center at the University of Minnesota
- United States Department of Defense
- University of Illinois at Chicago
- University of Minnesota
- University of Pennsylvania
- Weizmann Institute of Science