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Updated: Dec 10, 2025

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APOBEC3A catalyzes mutation and drives carcinogenesis in vivo

Emily K Law1,2,3,4, Rena Levin-Klein2,3,4, Matthew C Jarvis2,3,4

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

The Journal of Experimental Medicine
|September 2, 2020
PubMed

Insights

The DNA deaminase APOBEC3A drives tumor formation in mice, unlike other family members. Its distinct mutation signature in tumors provides evidence for its role in causing human cancers.

Area of Science:

  • Molecular Biology
  • Genetics
  • Cancer Research

Background:

  • The APOBEC3 family of DNA cytosine deaminases is a significant source of mutations in cancer.
  • The precise role of individual APOBEC3 members in tumorigenesis remains unclear.

Purpose of the Study:

  • To investigate the role of APOBEC3A in promoting cancer development.
  • To determine if APOBEC3A-induced mutations are characteristic of human cancers.

Main Methods:

  • Expression of human APOBEC3A in murine colon and liver tissues.
  • Analysis of tumor DNA sequences for APOBEC signature mutations.
  • Bioinformatic comparison of mutation signatures across species and datasets.

Main Results:

  • APOBEC3A expression significantly increased tumorigenesis in murine models.
  • APOBEC3B and other APOBEC3 members did not promote liver tumor formation.
  • APOBEC3A-expressing tumors exhibited characteristic TCA/T motif mutations.

Conclusions:

  • APOBEC3A acts as a driver of tumorigenesis.
  • The APOBEC3A mutation signature in murine tumors mirrors signatures found in human cancers.
  • APOBEC3A-catalyzed deamination is implicated in the development of multiple human cancers.

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