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EYA4 is inactivated biallelically at a high frequency in sporadic lung cancer and is associated with familial lung cancer risk

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 par...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4527534/
https://www.ncbi.nlm.nih.gov/pubmed/24096489
http://dx.doi.org/10.1038/onc.2013.396
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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.
author_facet 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.
author_sort Wilson, Ian M.
collection PubMed
description 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.
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spelling pubmed-45275342015-08-06 EYA4 is inactivated biallelically at a high frequency in sporadic lung cancer and is associated with familial lung cancer risk 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. Oncogene Article 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. 2013-10-07 2014-09-04 /pmc/articles/PMC4527534/ /pubmed/24096489 http://dx.doi.org/10.1038/onc.2013.396 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
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.
EYA4 is inactivated biallelically at a high frequency in sporadic lung cancer and is associated with familial lung cancer risk
title EYA4 is inactivated biallelically at a high frequency in sporadic lung cancer and is associated with familial lung cancer risk
title_full EYA4 is inactivated biallelically at a high frequency in sporadic lung cancer and is associated with familial lung cancer risk
title_fullStr EYA4 is inactivated biallelically at a high frequency in sporadic lung cancer and is associated with familial lung cancer risk
title_full_unstemmed EYA4 is inactivated biallelically at a high frequency in sporadic lung cancer and is associated with familial lung cancer risk
title_short EYA4 is inactivated biallelically at a high frequency in sporadic lung cancer and is associated with familial lung cancer risk
title_sort eya4 is inactivated biallelically at a high frequency in sporadic lung cancer and is associated with familial lung cancer risk
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4527534/
https://www.ncbi.nlm.nih.gov/pubmed/24096489
http://dx.doi.org/10.1038/onc.2013.396
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