EYA4 is inactivated biallelically at a high frequency in sporadic lung cancer and is associated with familial lung cancer risk
View/ Open
Author
Wilson, Ian M.
Vucic, Emily A.
Enfield, Katey S.S.
Thu, Kelsie L.
Zhang, Yu-An
Chari, Raj
Lockwood, William W.
Radulovich, Niki
Starczynowski, Daniel T.
Banáth, Judit P.
Zhang, May
Pusic, Andrea
Fuller, Megan
Lonergan, Kim M.
Rowbotham, David
Yee, John
English, John C.
Buys, Timon P.H.
Selamat, Suhaida A.
Laird-Offringa, Ite A.
Liu, Pengyuan
Anderson, Marshall
You, Ming
Tsao, Ming-Sound
Brown, Carolyn J.
Bennewith, Kevin L.
MacAulay, Calum E.
Karsan, Aly
Gazdar, Adi F.
Lam, Stephen
Lam, Wan L.
Note: Order does not necessarily reflect citation order of authors.
Published Version
https://doi.org/10.1038/onc.2013.396Metadata
Show full item recordCitation
Wilson, I. M., E. A. Vucic, K. S. Enfield, K. L. Thu, Y. Zhang, R. Chari, W. W. Lockwood, et al. 2015. “EYA4 is inactivated biallelically at a high frequency in sporadic lung cancer and is associated with familial lung cancer risk.” Oncogene 33 (36): 4464-4473. doi:10.1038/onc.2013.396. http://dx.doi.org/10.1038/onc.2013.396.Abstract
In an effort to identify novel biallelically inactivated tumor suppressor genes (TSG) in sporadic invasive and pre-invasive non-small cell lung cancer (NSCLC) genomes, we applied a comprehensive integrated multi-‘omics approach to investigate patient matched, paired NSCLC tumor and non-malignant parenchymal tissues. By surveying lung tumor genomes for genes concomitantly inactivated within individual tumors by multiple mechanisms, and by the frequency of disruption in tumors across multiple cohorts, we have identified a putative lung cancer TSG, Eyes Absent 4 (EYA4). EYA4 is frequently and concomitantly deleted, hypermethylated and underexpressed in multiple independent lung tumor data sets, in both major NSCLC subtypes, and in the earliest stages of lung cancer. We find not only that decreased EYA4 expression is associated with poor survival in sporadic lung cancers, but EYA4 SNPs are associated with increased familial cancer risk, consistent with EYA4’s proximity to the previously reported lung cancer susceptibility locus on 6q. Functionally, we find that EYA4 displays TSG-like properties with a role in modulating apoptosis and DNA repair. Cross examination of EYA4 expression across multiple tumor types suggests a cell type-specific tumorigenic role for EYA4, consistent with a tumor suppressor function in cancers of epithelial origin. This work shows a clear role for EYA4 as a putative TSG in NSCLC.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4527534/pdf/Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:21462027
Collections
- HMS Scholarly Articles [17922]
Contact administrator regarding this item (to report mistakes or request changes)