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

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.

journal_name

Nat Commun

journal_title

Nature communications

authors

Jalili P,Bowen D,Langenbucher A,Park S,Aguirre K,Corcoran RB,Fleischman AG,Lawrence MS,Zou L,Buisson R

doi

10.1038/s41467-020-16802-8

subject

Has Abstract

pub_date

2020-06-12 00:00:00

pages

2971

issue

1

issn

2041-1723

pii

10.1038/s41467-020-16802-8

journal_volume

11

pub_type

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