Quantification of ongoing APOBEC3A activity in tumor cells by monitoring RNA editing at hotspots.

Nature Communications
Pégah JaliliRémi Buisson

Abstract

APOBEC3A is a cytidine deaminase driving mutagenesis, DNA replication stress and DNA damage in cancer cells. While the APOBEC3A-induced vulnerability of cancers offers an opportunity for therapy, APOBEC3A protein and mRNA are difficult to quantify in tumors due to their low abundance. Here, we describe a quantitative and sensitive assay to measure the ongoing activity of APOBEC3A in tumors. Using hotspot RNA mutations identified from APOBEC3A-positive tumors and droplet digital PCR, we develop an assay to quantify the RNA-editing activity of APOBEC3A. This assay is superior to APOBEC3A protein- and mRNA-based assays in predicting the activity of APOBEC3A on DNA. Importantly, we demonstrate that the RNA mutation-based APOBEC3A assay is applicable to clinical samples from cancer patients. Our study presents a strategy to follow the dysregulation of APOBEC3A in tumors, providing opportunities to investigate the role of APOBEC3A in tumor evolution and to target the APOBEC3A-induced vulnerability in therapy.

References

Jan 12, 2010·Nature Structural & Molecular Biology·Mark D StengleinReuben S Harris
Apr 5, 2011·EMBO Reports·Sébastien LandryMatthew D Weitzman
Feb 8, 2013·Nature·Michael B BurnsReuben S Harris
Jul 16, 2013·Nature Genetics·Steven A RobertsDmitry A Gordenin
Aug 16, 2013·Nature·Ludmil B AlexandrovMichael R Stratton
Oct 25, 2013·Cancer Research·Brandon LeonardReuben S Harris
Apr 18, 2014·Methods in Molecular Biology·Francisco Bizouarn
Apr 22, 2015·Nature Communications·Shraddha SharmaBora E Baysal
Jun 21, 2015·Cancer Discovery·Charles SwantonReuben S Harris
Sep 13, 2015·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Larry M Karnitz, Lee Zou
Feb 27, 2016·Cell Cycle·Abby M GreenMatthew D Weitzman
May 3, 2016·Nature·Serena Nik-ZainalMichael R Stratton
Dec 20, 2016·Nature Structural & Molecular Biology·Ke ShiHideki Aihara
Apr 28, 2017·Cancers·Stuart RundleNicola J Curtin
May 3, 2018·Methods in Molecular Biology·David DobnikJana Žel
May 16, 2018·Scientific Reports·Tania V SilvasCelia A Schiffer
Aug 23, 2019·Annals of Laboratory Medicine·Hee Jung ChungYeo Min Yun

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Citations

Dec 10, 2020·Open Biology·Milaid Granadillo RodríguezLinda Chelico
Feb 18, 2021·RNA Biology·Małgorzata KurkowiakNatalia Marek-Trzonkowska
Mar 13, 2021·Nature Communications·Adam LangenbucherMichael S Lawrence
Aug 21, 2020·DNA Repair·Mia Petljak, John Maciejowski
Jul 3, 2021·Cells·Zachary W Kockler, Dmitry A Gordenin
Aug 18, 2021·Trends in Cell Biology·William HillCharles Swanton
May 29, 2021·Molecular Cancer Research : MCR·Kailiang ZhaoMeredith A Morgan
Aug 31, 2021·RSC Chemical Biology·Bingyao WangXiang Zhou

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Methods Mentioned

BETA
PCR
electrophoresis
Electrophoretic
Assay
deamination
transfections
transfection

Software Mentioned

QuantaSoft

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