Integration of gene dosage and gene expression in non-small cell lung cancer, identification of HSP90 as potential target.

<h4>Background</h4>Lung cancer causes approximately 1.2 million deaths per year worldwide, and non-small cell lung cancer (NSCLC) represents 85% of all lung cancers. Understanding the molecular events in non-small cell lung cancer (NSCLC) is essential to improve early diagnosis and treat...

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Autores principales: Mariëlle I Gallegos Ruiz, Karijn Floor, Paul Roepman, José A Rodriguez, Gerrit A Meijer, Wolter J Mooi, Ewa Jassem, Jacek Niklinski, Thomas Muley, Nico van Zandwijk, Egbert F Smit, Kristin Beebe, Len Neckers, Bauke Ylstra, Giuseppe Giaccone
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Publicado: Public Library of Science (PLoS) 2008
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spelling oai:doaj.org-article:968fb65e51f24ad8b7bfe4a80bbddea92021-11-25T06:13:13ZIntegration of gene dosage and gene expression in non-small cell lung cancer, identification of HSP90 as potential target.1932-620310.1371/journal.pone.0001722https://doaj.org/article/968fb65e51f24ad8b7bfe4a80bbddea92008-03-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18320023/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Lung cancer causes approximately 1.2 million deaths per year worldwide, and non-small cell lung cancer (NSCLC) represents 85% of all lung cancers. Understanding the molecular events in non-small cell lung cancer (NSCLC) is essential to improve early diagnosis and treatment for this disease.<h4>Methodology and principal findings</h4>In an attempt to identify novel NSCLC related genes, we performed a genome-wide screening of chromosomal copy number changes affecting gene expression using microarray based comparative genomic hybridization and gene expression arrays on 32 radically resected tumor samples from stage I and II NSCLC patients. An integrative analysis tool was applied to determine whether chromosomal copy number affects gene expression. We identified a deletion on 14q32.2-33 as a common alteration in NSCLC (44%), which significantly influenced gene expression for HSP90, residing on 14q32. This deletion was correlated with better overall survival (P = 0.008), survival was also longer in patients whose tumors had low expression levels of HSP90. We extended the analysis to three independent validation sets of NSCLC patients, and confirmed low HSP90 expression to be related with longer overall survival (P = 0.003, P = 0.07 and P = 0.04). Furthermore, in vitro treatment with an HSP90 inhibitor had potent antiproliferative activity in NSCLC cell lines.<h4>Conclusions</h4>We suggest that targeting HSP90 will have clinical impact for NSCLC patients.Mariëlle I Gallegos RuizKarijn FloorPaul RoepmanJosé A RodriguezGerrit A MeijerWolter J MooiEwa JassemJacek NiklinskiThomas MuleyNico van ZandwijkEgbert F SmitKristin BeebeLen NeckersBauke YlstraGiuseppe GiacconePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 3, Iss 3, p e0001722 (2008)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Mariëlle I Gallegos Ruiz
Karijn Floor
Paul Roepman
José A Rodriguez
Gerrit A Meijer
Wolter J Mooi
Ewa Jassem
Jacek Niklinski
Thomas Muley
Nico van Zandwijk
Egbert F Smit
Kristin Beebe
Len Neckers
Bauke Ylstra
Giuseppe Giaccone
Integration of gene dosage and gene expression in non-small cell lung cancer, identification of HSP90 as potential target.
description <h4>Background</h4>Lung cancer causes approximately 1.2 million deaths per year worldwide, and non-small cell lung cancer (NSCLC) represents 85% of all lung cancers. Understanding the molecular events in non-small cell lung cancer (NSCLC) is essential to improve early diagnosis and treatment for this disease.<h4>Methodology and principal findings</h4>In an attempt to identify novel NSCLC related genes, we performed a genome-wide screening of chromosomal copy number changes affecting gene expression using microarray based comparative genomic hybridization and gene expression arrays on 32 radically resected tumor samples from stage I and II NSCLC patients. An integrative analysis tool was applied to determine whether chromosomal copy number affects gene expression. We identified a deletion on 14q32.2-33 as a common alteration in NSCLC (44%), which significantly influenced gene expression for HSP90, residing on 14q32. This deletion was correlated with better overall survival (P = 0.008), survival was also longer in patients whose tumors had low expression levels of HSP90. We extended the analysis to three independent validation sets of NSCLC patients, and confirmed low HSP90 expression to be related with longer overall survival (P = 0.003, P = 0.07 and P = 0.04). Furthermore, in vitro treatment with an HSP90 inhibitor had potent antiproliferative activity in NSCLC cell lines.<h4>Conclusions</h4>We suggest that targeting HSP90 will have clinical impact for NSCLC patients.
format article
author Mariëlle I Gallegos Ruiz
Karijn Floor
Paul Roepman
José A Rodriguez
Gerrit A Meijer
Wolter J Mooi
Ewa Jassem
Jacek Niklinski
Thomas Muley
Nico van Zandwijk
Egbert F Smit
Kristin Beebe
Len Neckers
Bauke Ylstra
Giuseppe Giaccone
author_facet Mariëlle I Gallegos Ruiz
Karijn Floor
Paul Roepman
José A Rodriguez
Gerrit A Meijer
Wolter J Mooi
Ewa Jassem
Jacek Niklinski
Thomas Muley
Nico van Zandwijk
Egbert F Smit
Kristin Beebe
Len Neckers
Bauke Ylstra
Giuseppe Giaccone
author_sort Mariëlle I Gallegos Ruiz
title Integration of gene dosage and gene expression in non-small cell lung cancer, identification of HSP90 as potential target.
title_short Integration of gene dosage and gene expression in non-small cell lung cancer, identification of HSP90 as potential target.
title_full Integration of gene dosage and gene expression in non-small cell lung cancer, identification of HSP90 as potential target.
title_fullStr Integration of gene dosage and gene expression in non-small cell lung cancer, identification of HSP90 as potential target.
title_full_unstemmed Integration of gene dosage and gene expression in non-small cell lung cancer, identification of HSP90 as potential target.
title_sort integration of gene dosage and gene expression in non-small cell lung cancer, identification of hsp90 as potential target.
publisher Public Library of Science (PLoS)
publishDate 2008
url https://doaj.org/article/968fb65e51f24ad8b7bfe4a80bbddea9
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