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A compendium of Amplification-Related Gain Of Sensitivity genes in human cancer

Author

Listed:
  • Veronica Rendo

    (Dana-Farber Cancer Institute
    Dana-Farber Cancer Institute
    Harvard Medical School
    Broad Institute of Harvard and MIT)

  • Michael Schubert

    (The Netherlands Cancer Institute
    University Medical Center Groningen
    Helmholtz Munich
    Medical University of Innsbruck)

  • Nicholas Khuu

    (Dana-Farber Cancer Institute
    Dana-Farber Cancer Institute
    Broad Institute of Harvard and MIT)

  • Maria F. Suarez Peredo Rodriguez

    (University Medical Center Groningen)

  • Declan Whyte

    (University Medical Center Groningen)

  • Xiao Ling

    (University Medical Center Groningen)

  • Anouk Brink

    (University Medical Center Groningen)

  • Kaimeng Huang

    (Broad Institute of Harvard and MIT
    Dana-Farber Cancer Institute)

  • Michelle Swift

    (Dana-Farber Cancer Institute)

  • Yizhou He

    (Broad Institute of Harvard and MIT
    Dana-Farber Cancer Institute)

  • Johanna Zerbib

    (Tel Aviv University)

  • Ross Smith

    (Uppsala University)

  • Jonne Raaijmakers

    (The Netherlands Cancer Institute)

  • Pratiti Bandopadhayay

    (Harvard Medical School
    Broad Institute of Harvard and MIT
    Dana-Farber Cancer Institute)

  • Lillian M. Guenther

    (Department of Oncology)

  • Justin H. Hwang

    (University of Minnesota)

  • Amanda Iniguez

    (Perelman School of Medicine at the University of Pennsylvania)

  • Susan Moody

    (Dana-Farber Cancer Institute
    Harvard Medical School
    Broad Institute of Harvard and MIT)

  • Ji-Heui Seo

    (Dana-Farber Cancer Institute)

  • Elizabeth H. Stover

    (Dana-Farber Cancer Institute
    Harvard Medical School
    Broad Institute of Harvard and MIT)

  • Levi Garraway

    (Dana-Farber Cancer Institute
    Broad Institute of Harvard and MIT)

  • William C. Hahn

    (Dana-Farber Cancer Institute
    Harvard Medical School
    Broad Institute of Harvard and MIT)

  • Kimberly Stegmaier

    (Harvard Medical School
    Broad Institute of Harvard and MIT
    Dana-Farber Cancer Institute)

  • René H. Medema

    (The Netherlands Cancer Institute)

  • Dipanjan Chowdhury

    (Broad Institute of Harvard and MIT
    Dana-Farber Cancer Institute)

  • Maria Colomé-Tatché

    (Helmholtz Munich
    Ludwig Maximilians University)

  • Uri Ben-David

    (Tel Aviv University)

  • Rameen Beroukhim

    (Dana-Farber Cancer Institute
    Dana-Farber Cancer Institute
    Harvard Medical School
    Broad Institute of Harvard and MIT)

  • Floris Foijer

    (University Medical Center Groningen)

Abstract

While the effect of amplification-induced oncogene expression in cancer is known, the impact of copy-number gains on “bystander” genes is less understood. We create a comprehensive map of dosage compensation in cancer by integrating expression and copy number profiles from over 8000 tumors in The Cancer Genome Atlas and cell lines from the Cancer Cell Line Encyclopedia. Additionally, we analyze 17 cancer open reading frame screens to identify genes toxic to cancer cells when overexpressed. Combining these approaches, we propose a class of ‘Amplification-Related Gain Of Sensitivity’ (ARGOS) genes located in commonly amplified regions, yet expressed at lower levels than expected by their copy number, and toxic when overexpressed. We validate RBM14 as an ARGOS gene in lung and breast cancer cells, and suggest a toxicity mechanism involving altered DNA damage response and STING signaling. We additionally observe increased patient survival in a radiation-treated cancer cohort with RBM14 amplification.

Suggested Citation

  • Veronica Rendo & Michael Schubert & Nicholas Khuu & Maria F. Suarez Peredo Rodriguez & Declan Whyte & Xiao Ling & Anouk Brink & Kaimeng Huang & Michelle Swift & Yizhou He & Johanna Zerbib & Ross Smith, 2025. "A compendium of Amplification-Related Gain Of Sensitivity genes in human cancer," Nature Communications, Nature, vol. 16(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56301-2
    DOI: 10.1038/s41467-025-56301-2
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