We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Quantification of ongoing APOBEC3A activity in tumor cells by monitoring RNA editing at hotspots.
- Authors
Jalili, Pégah; Bowen, Danae; Langenbucher, Adam; Park, Shinho; Aguirre, Kevin; Corcoran, Ryan B.; Fleischman, Angela G.; Lawrence, Michael S.; Zou, Lee; Buisson, Rémi
- 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. The DNA cytosine deaminases APOBEC3A and APOBEC3B have emerged from cancer genomics studies as drivers of mutation in cancers and tumor heterogeneity. Here the authors present a computational approach to identify the RNA mutations specifically driven by APOBEC3A, and developed an RNA mutation-based assay to quantify ongoing APOBEC3A activity in tumor cells.
- Subjects
RNA editing; CYTIDINE deaminase; DNA replication; DNA damage; CANCER patients
- Publication
Nature Communications, 2020, Vol 11, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-020-16802-8