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

Author

Listed:
  • Pégah Jalili

    (University of California Irvine)

  • Danae Bowen

    (University of California Irvine)

  • Adam Langenbucher

    (Harvard Medical School)

  • Shinho Park

    (University of California Irvine)

  • Kevin Aguirre

    (University of California Irvine)

  • Ryan B. Corcoran

    (Harvard Medical School)

  • Angela G. Fleischman

    (University of California Irvine)

  • Michael S. Lawrence

    (Harvard Medical School
    Harvard Medical School
    Broad Institute of Harvard and MIT)

  • Lee Zou

    (Harvard Medical School
    Harvard Medical School)

  • Rémi Buisson

    (University of California Irvine
    Harvard Medical School)

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.

Suggested Citation

  • Pégah Jalili & Danae Bowen & Adam Langenbucher & Shinho Park & Kevin Aguirre & Ryan B. Corcoran & Angela G. Fleischman & Michael S. Lawrence & Lee Zou & Rémi Buisson, 2020. "Quantification of ongoing APOBEC3A activity in tumor cells by monitoring RNA editing at hotspots," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-16802-8
    DOI: 10.1038/s41467-020-16802-8
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    Cited by:

    1. Ambrocio Sanchez & Pedro Ortega & Ramin Sakhtemani & Lavanya Manjunath & Sunwoo Oh & Elodie Bournique & Alexandrea Becker & Kyumin Kim & Cameron Durfee & Nuri Alpay Temiz & Xiaojiang S. Chen & Reuben , 2024. "Mesoscale DNA features impact APOBEC3A and APOBEC3B deaminase activity and shape tumor mutational landscapes," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Stefan Harjes & Harikrishnan M. Kurup & Amanda E. Rieffer & Maitsetseg Bayarjargal & Jana Filitcheva & Yongdong Su & Tracy K. Hale & Vyacheslav V. Filichev & Elena Harjes & Reuben S. Harris & Geoffrey, 2023. "Structure-guided inhibition of the cancer DNA-mutating enzyme APOBEC3A," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

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