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Nat Commun. 2019 Nov 28;10(1):5438. doi: 10.1038/s41467-019-13295-y.

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

Author information

1
British Columbia Cancer Research Centre, Vancouver, BC, Canada. katey.enfield@crick.ac.uk.
2
British Columbia Cancer Research Centre, Vancouver, BC, Canada.
3
Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
4
Dalhousie University, Halifax, NS, Canada.
5
Deeley Research Centre, Victoria, BC, Canada.
6
Vancouver General Hospital, Vancouver, BC, Canada.
7
Frederick National Lab for Cancer Research, Laboratory Animal Sciences Program, Frederick, MD, USA.
8
Krembil Research Institute, University Health Network, Toronto, ON, Canada.
9
British Columbia Cancer Research Centre, Vancouver, BC, Canada. wanlam@bccrc.ca.

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.

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