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Epithelial tumor suppressor ELF3 is a lineage-specific amplified oncogene in lung adenocarcinoma

Author

Listed:
  • Katey S. S. Enfield

    (British Columbia Cancer Research Centre)

  • Erin A. Marshall

    (British Columbia Cancer Research Centre)

  • Christine Anderson

    (British Columbia Cancer Research Centre)

  • Kevin W. Ng

    (British Columbia Cancer Research Centre)

  • Sara Rahmati

    (University of Toronto)

  • Zhaolin Xu

    (Dalhousie University)

  • Megan Fuller

    (British Columbia Cancer Research Centre)

  • Katy Milne

    (Deeley Research Centre)

  • Daniel Lu

    (British Columbia Cancer Research Centre)

  • Rocky Shi

    (British Columbia Cancer Research Centre)

  • David A. Rowbotham

    (British Columbia Cancer Research Centre)

  • Daiana D. Becker-Santos

    (British Columbia Cancer Research Centre)

  • Fraser D. Johnson

    (British Columbia Cancer Research Centre)

  • John C. English

    (Vancouver General Hospital)

  • Calum E. MacAulay

    (British Columbia Cancer Research Centre)

  • Stephen Lam

    (British Columbia Cancer Research Centre)

  • William W. Lockwood

    (British Columbia Cancer Research Centre)

  • Raj Chari

    (Frederick National Lab for Cancer Research, Laboratory Animal Sciences Program)

  • Aly Karsan

    (British Columbia Cancer Research Centre)

  • Igor Jurisica

    (University Health Network)

  • Wan L. Lam

    (British Columbia Cancer Research Centre)

Abstract

Gene function in cancer is often cell type-specific. The epithelial cell-specific transcription factor ELF3 is a documented tumor suppressor in many epithelial tumors yet displays oncogenic properties in others. Here, we show that ELF3 is an oncogene in the adenocarcinoma subtype of lung cancer (LUAD), providing genetic, functional, and clinical evidence of subtype specificity. We discover a region of focal amplification at chromosome 1q32.1 encompassing the ELF3 locus in LUAD which is absent in the squamous subtype. Gene dosage and promoter hypomethylation affect the locus in up to 80% of LUAD analyzed. ELF3 expression was required for tumor growth and a pan-cancer expression network analysis supports its subtype and tissue specificity. We further show that ELF3 displays strong prognostic value in LUAD but not LUSC. We conclude that, contrary to many other tumors of epithelial origin, ELF3 is an oncogene and putative therapeutic target in LUAD.

Suggested Citation

  • Katey S. S. Enfield & Erin A. Marshall & Christine Anderson & Kevin W. Ng & Sara Rahmati & Zhaolin Xu & Megan Fuller & Katy Milne & Daniel Lu & Rocky Shi & David A. Rowbotham & Daiana D. Becker-Santos, 2019. "Epithelial tumor suppressor ELF3 is a lineage-specific amplified oncogene in lung adenocarcinoma," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13295-y
    DOI: 10.1038/s41467-019-13295-y
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