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Annual Review of Genetics

Volume 56, 2022

APOBEC-Induced Mutagenesis in Cancer

Abstract

The initiation, progression, and relapse of cancers often result from mutations occurring within somatic cells. Consequently, processes that elevate mutation rates accelerate carcinogenesis and hinder the development of long-lasting therapeutics. Recent sequencing of human cancer genomes has identified patterns of mutations, termed mutation signatures, many of which correspond to specific environmentally induced and endogenous mutation processes. Some of the most frequently observed mutation signatures are caused by dysregulated activity of APOBECs, which deaminate cytidines in single-stranded DNA at specific sequence motifs causing C-to-T and C-to-G substitutions. In humans, APOBEC-generated genetic heterogeneity in tumor cells contributes to carcinogenesis, metastasis, and resistance to therapeutics. Here, we review the current understanding of APOBECs’ role in cancer mutagenesis and impact on disease and the biological processes that influence APOBEC mutagenic capacity.

Keyword(s): APOBEC, cancer, cytidine deaminase, cytidine deamination, mutation, mutation signature
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2022-11-30
2024-05-09
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APOBEC-Induced Mutagenesis in Cancer
Annual Review of Genetics 56, 229 (2022); https://doi.org/10.1146/annurev-genet-072920-035840
/content/journals/10.1146/annurev-genet-072920-035840
/content/journals/10.1146/annurev-genet-072920-035840
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