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; Wan L. Lam

doi:10.1038/s41467-019-13295-y

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 JurisicaWan L. Lam

Medicine

Producción científica: Contribución a una revista › Artículo › revisión exhaustiva

49 Citas (Scopus)

Resumen

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.

Idioma original	English
Número de artículo	5438
Publicación	Nature Communications
Volumen	10
N.º	1
DOI	https://doi.org/10.1038/s41467-019-13295-y
Estado	Published - dic. 1 2019

Nota bibliográfica

Funding Information:
This work was supported by grants from the Canadian Institutes for Health Research (CIHR, FDN-143345). I.J. and computational analysis was supported in part by the Canada Research Chair Program (CRC #225404), Ontario Research Fund (#34876), Natural Sciences Research Council (NSERC #203475), Canada Foundation for Innovation (CFI #203373, #30865), Krembil Foundation and IBM. The A.K. laboratory is supported by grants from CIHR and the Terry Fox Research Institute, and A.K. is supported by a John Auston BC Cancer Foundation Clinical Investigator Award. W.W.L. is a Michael Smith Foundation for Health Research Biomedical Research Scholar. K.S.S.E., D.A.R. and F.D.J. were supported by CIHR Frederick Banting and Charles Best Canada Graduate Scholarships and fellowships from the University of British Columbia (UBC). E.A.M. and D.D.B.S. are Vanier Canada Graduate Scholars and received support from UBC. The results shown here are in part based upon data generated by the TCGA Research Network: http://cancergenome.nih.gov/.

Publisher Copyright:
© 2019, The Author(s).

ASJC Scopus Subject Areas

General Chemistry
General Biochemistry,Genetics and Molecular Biology
General Physics and Astronomy

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Enfield, K. S. S., Marshall, E. A., Anderson, C., Ng, K. W., Rahmati, S., Xu, Z., Fuller, M., Milne, K., Lu, D., Shi, R., Rowbotham, D. A., Becker-Santos, D. D., Johnson, F. D., English, J. C., MacAulay, C. E., Lam, S., Lockwood, W. W., Chari, R., Karsan, A., ... Lam, W. L. (2019). Epithelial tumor suppressor ELF3 is a lineage-specific amplified oncogene in lung adenocarcinoma. Nature Communications, 10(1), Artículo 5438. https://doi.org/10.1038/s41467-019-13295-y

Enfield, KSS, Marshall, EA, Anderson, C, Ng, KW, Rahmati, S, Xu, Z, Fuller, M, Milne, K, Lu, D, Shi, R, Rowbotham, DA, Becker-Santos, DD, Johnson, FD, English, JC, MacAulay, CE, Lam, S, Lockwood, WW, Chari, R, Karsan, A, Jurisica, I & Lam, WL 2019, 'Epithelial tumor suppressor ELF3 is a lineage-specific amplified oncogene in lung adenocarcinoma', Nature Communications, vol. 10, n.º 1, 5438. https://doi.org/10.1038/s41467-019-13295-y

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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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AU - Jurisica, Igor

AU - Lam, Wan L.

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

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