Clinical Implications of APOBEC3-Mediated Mutagenesis in Breast Cancer

Pieter A Roelofs; John W M Martens; Reuben S Harris; Paul N Span

doi:10.1158/1078-0432.CCR-22-2861

Clinical Implications of APOBEC3-Mediated Mutagenesis in Breast Cancer

Pieter A Roelofs
, John W M Martens
, Reuben S Harris
, Paul N Span^*

^*Corresponding author for this work

Medical Oncology

Radboud University Medical Center
University of Minnesota

Research output: Contribution to journal › Review article › Academic › peer-review

18 Citations (Scopus)

Abstract

Over recent years, members of the APOBEC3 family of cytosine deaminases have been implicated in increased cancer genome mutagenesis, thereby contributing to intratumor and intertumor genomic heterogeneity and therapy resistance in, among others, breast cancer. Understanding the available methods for clinical detection of these enzymes, the conditions required for their (dysregulated) expression, the clinical impact they have, and the clinical implications they may offer is crucial in understanding the current impact of APOBEC3-mediated mutagenesis in breast cancer. Here, we provide a comprehensive review of recent developments in the detection of APOBEC3-mediated mutagenesis and responsible APOBEC3 enzymes, summarize the pathways that control their expression, and explore the clinical ramifications and opportunities they pose. We propose that APOBEC3-mediated mutagenesis can function as a helpful predictive biomarker in several standard-of-care breast cancer treatment plans and may be a novel target for treatment.

Original language	English
Pages (from-to)	1658-1659
Number of pages	2
Journal	Clinical Cancer Research : an official journal of the American Association for Cancer Research
Volume	29
Issue number	9
DOIs	https://doi.org/10.1158/1078-0432.CCR-22-2861
Publication status	Published - 1 May 2023

Bibliographical note

Funding Information:
We want to extend our gratitude to Wilke Castelijns, MSc, for helpful suggestions during the early conceptualization phase of this review. We also thank Bojana Stefanovska, PhD, and Anya Normandeau, BA, for helpful feedback. We thank Dr. Prokopios Argyris for the IHC image of the breast cancer specimen in Figure 1. This work was supported, in part, by the KWF Dutch Cancer Society (KWF10270, to J.W.M. Martens, P.N. Span, and R.S. Harris) and by the NCI (P01-CA234228, to R.S. Harris). R.S. Harris is the Ewing Halsell President’s Council Distinguished Chair, a CPRIT Scholar, and an Investigator of the Howard Hughes Medical Institute at University of Texas Health San Antonio. None of the funding agencies had any role in conceptualization, study design, data collection, interpretation of results, or the decision to submit this work for publication.

Funding Information:
This work was supported, in part, by the KWF Dutch Cancer Society (KWF10270, to J.W.M. Martens, P.N. Span, and R.S. Harris) and by the NCI (P01-CA234228, to R.S. Harris). R.S. Harris is the Ewing Halsell President’s Council Distinguished Chair, a CPRIT Scholar, and an Investigator of the Howard Hughes Medical Institute at University of Texas Health San Antonio. None of the funding agencies had any role in conceptualization, study design, data collection, interpretation of results, or the decision to submit this work for publication.

Funding Information:
J.W.M. Martens reports grants from The Dutch Cancer Society during the conduct of the study as well as personal fees from Novartis; other support from Roche; and grants from The Dutch Cancer Society, The Dutch Organisation of

Publisher Copyright:
©2022 American Association for Cancer Research.

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10.1158/1078-0432.CCR-22-2861

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10159886/pdf/nihms-1853784.pdf

Cite this

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title = "Clinical Implications of APOBEC3-Mediated Mutagenesis in Breast Cancer",

abstract = "Over recent years, members of the APOBEC3 family of cytosine deaminases have been implicated in increased cancer genome mutagenesis, thereby contributing to intratumor and intertumor genomic heterogeneity and therapy resistance in, among others, breast cancer. Understanding the available methods for clinical detection of these enzymes, the conditions required for their (dysregulated) expression, the clinical impact they have, and the clinical implications they may offer is crucial in understanding the current impact of APOBEC3-mediated mutagenesis in breast cancer. Here, we provide a comprehensive review of recent developments in the detection of APOBEC3-mediated mutagenesis and responsible APOBEC3 enzymes, summarize the pathways that control their expression, and explore the clinical ramifications and opportunities they pose. We propose that APOBEC3-mediated mutagenesis can function as a helpful predictive biomarker in several standard-of-care breast cancer treatment plans and may be a novel target for treatment.",

author = "Roelofs, \{Pieter A\} and Martens, \{John W M\} and Harris, \{Reuben S\} and Span, \{Paul N\}",

note = "Funding Information: We want to extend our gratitude to Wilke Castelijns, MSc, for helpful suggestions during the early conceptualization phase of this review. We also thank Bojana Stefanovska, PhD, and Anya Normandeau, BA, for helpful feedback. We thank Dr. Prokopios Argyris for the IHC image of the breast cancer specimen in Figure 1. This work was supported, in part, by the KWF Dutch Cancer Society (KWF10270, to J.W.M. Martens, P.N. Span, and R.S. Harris) and by the NCI (P01-CA234228, to R.S. Harris). R.S. Harris is the Ewing Halsell President{\textquoteright}s Council Distinguished Chair, a CPRIT Scholar, and an Investigator of the Howard Hughes Medical Institute at University of Texas Health San Antonio. None of the funding agencies had any role in conceptualization, study design, data collection, interpretation of results, or the decision to submit this work for publication. Funding Information: This work was supported, in part, by the KWF Dutch Cancer Society (KWF10270, to J.W.M. Martens, P.N. Span, and R.S. Harris) and by the NCI (P01-CA234228, to R.S. Harris). R.S. Harris is the Ewing Halsell President{\textquoteright}s Council Distinguished Chair, a CPRIT Scholar, and an Investigator of the Howard Hughes Medical Institute at University of Texas Health San Antonio. None of the funding agencies had any role in conceptualization, study design, data collection, interpretation of results, or the decision to submit this work for publication. Funding Information: J.W.M. Martens reports grants from The Dutch Cancer Society during the conduct of the study as well as personal fees from Novartis; other support from Roche; and grants from The Dutch Cancer Society, The Dutch Organisation of Publisher Copyright: {\textcopyright}2022 American Association for Cancer Research.",

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AU - Roelofs, Pieter A

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AU - Harris, Reuben S

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N1 - Funding Information: We want to extend our gratitude to Wilke Castelijns, MSc, for helpful suggestions during the early conceptualization phase of this review. We also thank Bojana Stefanovska, PhD, and Anya Normandeau, BA, for helpful feedback. We thank Dr. Prokopios Argyris for the IHC image of the breast cancer specimen in Figure 1. This work was supported, in part, by the KWF Dutch Cancer Society (KWF10270, to J.W.M. Martens, P.N. Span, and R.S. Harris) and by the NCI (P01-CA234228, to R.S. Harris). R.S. Harris is the Ewing Halsell President’s Council Distinguished Chair, a CPRIT Scholar, and an Investigator of the Howard Hughes Medical Institute at University of Texas Health San Antonio. None of the funding agencies had any role in conceptualization, study design, data collection, interpretation of results, or the decision to submit this work for publication. Funding Information: This work was supported, in part, by the KWF Dutch Cancer Society (KWF10270, to J.W.M. Martens, P.N. Span, and R.S. Harris) and by the NCI (P01-CA234228, to R.S. Harris). R.S. Harris is the Ewing Halsell President’s Council Distinguished Chair, a CPRIT Scholar, and an Investigator of the Howard Hughes Medical Institute at University of Texas Health San Antonio. None of the funding agencies had any role in conceptualization, study design, data collection, interpretation of results, or the decision to submit this work for publication. Funding Information: J.W.M. Martens reports grants from The Dutch Cancer Society during the conduct of the study as well as personal fees from Novartis; other support from Roche; and grants from The Dutch Cancer Society, The Dutch Organisation of Publisher Copyright: ©2022 American Association for Cancer Research.

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N2 - Over recent years, members of the APOBEC3 family of cytosine deaminases have been implicated in increased cancer genome mutagenesis, thereby contributing to intratumor and intertumor genomic heterogeneity and therapy resistance in, among others, breast cancer. Understanding the available methods for clinical detection of these enzymes, the conditions required for their (dysregulated) expression, the clinical impact they have, and the clinical implications they may offer is crucial in understanding the current impact of APOBEC3-mediated mutagenesis in breast cancer. Here, we provide a comprehensive review of recent developments in the detection of APOBEC3-mediated mutagenesis and responsible APOBEC3 enzymes, summarize the pathways that control their expression, and explore the clinical ramifications and opportunities they pose. We propose that APOBEC3-mediated mutagenesis can function as a helpful predictive biomarker in several standard-of-care breast cancer treatment plans and may be a novel target for treatment.

AB - Over recent years, members of the APOBEC3 family of cytosine deaminases have been implicated in increased cancer genome mutagenesis, thereby contributing to intratumor and intertumor genomic heterogeneity and therapy resistance in, among others, breast cancer. Understanding the available methods for clinical detection of these enzymes, the conditions required for their (dysregulated) expression, the clinical impact they have, and the clinical implications they may offer is crucial in understanding the current impact of APOBEC3-mediated mutagenesis in breast cancer. Here, we provide a comprehensive review of recent developments in the detection of APOBEC3-mediated mutagenesis and responsible APOBEC3 enzymes, summarize the pathways that control their expression, and explore the clinical ramifications and opportunities they pose. We propose that APOBEC3-mediated mutagenesis can function as a helpful predictive biomarker in several standard-of-care breast cancer treatment plans and may be a novel target for treatment.

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DO - 10.1158/1078-0432.CCR-22-2861

M3 - Review article

C2 - 36478188

SN - 1078-0432

VL - 29

SP - 1658

EP - 1659

JO - Clinical Cancer Research : an official journal of the American Association for Cancer Research

JF - Clinical Cancer Research : an official journal of the American Association for Cancer Research

IS - 9

ER -

Clinical Implications of APOBEC3-Mediated Mutagenesis in Breast Cancer

Abstract

Bibliographical note

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