APOBEC3A catalyzes mutation and drives carcinogenesis in vivo-Reference-Cited by-同舟云学术

APOBEC3A catalyzes mutation and drives carcinogenesis in vivo

Published:2020-09-01 Issue:12 Volume:217 Page:
ISSN:0022-1007
Container-title:Journal of Experimental Medicine
language:en
Short-container-title:

Author:

Law Emily K.¹²³⁴^ORCID,Levin-Klein Rena²³⁴^ORCID,Jarvis Matthew C.²³⁴^ORCID,Kim Hyoung⁵^ORCID,Argyris Prokopios P.¹²³⁴⁶^ORCID,Carpenter Michael A.¹²³⁴^ORCID,Starrett Gabriel J.²³⁴⁷^ORCID,Temiz Nuri A.²⁸^ORCID,Larson Lindsay K.²³⁴^ORCID,Durfee Cameron²³⁴^ORCID,Burns Michael B.²³⁴⁹^ORCID,Vogel Rachel I.²¹⁰^ORCID,Stavrou Spyridon⁵¹¹^ORCID,Aguilera Alexya N.¹¹^ORCID,Wagner Sandra²¹²^ORCID,Largaespada David A.²¹²^ORCID,Starr Timothy K.²¹⁰^ORCID,Ross Susan R.⁵¹¹^ORCID,Harris Reuben S.¹²³⁴^ORCID

Affiliation:

1. Howard Hughes Medical Institute, University of Minnesota, Minneapolis, MN

2. Masonic Cancer Center, University of Minnesota, Minneapolis, MN

3. Institute for Molecular Virology, University of Minnesota, Minneapolis, MN

4. Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN

5. Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA

6. Division of Oral and Maxillofacial Pathology, School of Dentistry, University of Minnesota, Minneapolis, MN

7. Laboratory of Cellular Oncology, National Cancer Institute, National Institutes of Health, Bethesda, MD

8. Institute for Health Informatics, University of Minnesota, Minneapolis, MN

9. Department of Biology, Loyola University, Chicago, IL

10. Department of Obstetrics, Gynecology, and Women’s Health, University of Minnesota, Minneapolis, MN

11. Department of Microbiology and Immunology, College of Medicine, University of Illinois at Chicago, Chicago, IL

12. Department of Pediatrics, University of Minnesota, Minneapolis, MN

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.

Funder

National Cancer Institute

National Institute of Allergy and Infectious Diseases

National Institute on Aging

University of Minnesota College of Biological Sciences and Academic Health Center

Randy Shaver Cancer Research and Community Fund

Masonic Cancer Center Translational Working Group

Mezin-Koats Colorectal Cancer Research Fund

National Institutes of Health

Weizmann Institute of Science

US Department of Defense

Howard Hughes Medical Institute