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

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, Fraser D. Johnson, John C. English, Calum E. MacAulay, Stephen Lam, William W. Lockwood, Raj Chari, Aly Karsan, Igor Jurisica and Wan L. Lam ()
Additional contact information
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

Nature Communications, 2019, vol. 10, issue 1, 1-13

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-13295-y

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