Microarray analysis of gene expression in vestibular schwannomas reveals SPP1/MET signaling pathway and androgen receptor deregulation

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dc.contributor.author Torres-Martín, Miguel
dc.contributor.author Lassaletta, Luis
dc.contributor.author San-Román-Montero, Jesús M.
dc.contributor.author De Campos, José Maria
dc.contributor.author Isla-Guerrero, Alberto
dc.contributor.author Gavilan Bouzas, Javier
dc.contributor.author Meléndez, Bárbara
dc.contributor.author Pinto, Giovanny R.
dc.contributor.author Burbano, Rommel Rodríguez Rodríguez
dc.contributor.author Castresana, Javier Sáez
dc.contributor.author Rey, Juan Antonio
dc.contributor.other UAM. Departamento de Cirugía es_ES
dc.date.accessioned 2015-02-05T10:41:57Z
dc.date.available 2015-02-05T10:41:57Z
dc.date.issued 2013-03-01
dc.identifier.citation International Journal of Oncology 42.3 (2013): 848-862 es_ES
dc.identifier.issn 1019-6439 (print) en_US
dc.identifier.issn 1791-2423 (online) en_US
dc.identifier.uri http://hdl.handle.net/10486/663571
dc.description.abstract Vestibular schwannomas are benign neoplasms that arise from the vestibular nerve. The hallmark of these tumors is the biallelic inactivation of neurofibromin 2 (NF2). Transcriptomic alterations, such as the neuregulin 1 (NRG1)/ErbB2 pathway, have been described in schwannomas. In this study, we performed a whole transcriptome analysis in 31 vestibular schwannomas and 9 control nerves in the Affymetrix Gene 1.0 ST platform, validated by quantitative real-time PCR (qRT-PCR) using TaqMan Low Density arrays. We performed a mutational analysis of NF2 by PCR̸denaturing high-performance liquid chromatography (dHPLC) and multiplex ligation-dependent probe amplification (MLPA), as well as a microsatellite marker analysis of the loss of heterozygosity (LOH) of chromosome 22q. The microarray analysis demonstrated that 1,516 genes were deregulated and 48 of the genes were validated by qRT-PCR. At least 2 genetic hits (allelic loss and/or gene mutation) in NF2 were found in 16 tumors, seven cases showed 1 hit and 8 tumors showed no NF2 alteration. MET and associated genes, such as integrin, alpha 4 (ITGA4)̸B6, PLEXNB3/SEMA5 and caveolin-1 (CAV1) showed a clear deregulation in vestibular schwannomas. In addition, androgen receptor (AR) downregulation may denote a hormonal effect or cause in this tumor. Furthermore, the osteopontin gene (SPP1), which is involved in merlin protein degradation, was upregulated, which suggests that this mechanism may also exert a pivotal role in schwannoma merlin depletion. Finally, no major differences were observed among tumors of different size, histological type or NF2 status, which suggests that, at the mRNA level, all schwannomas, regardless of their molecular and clinical characteristics, may share common features that can be used in their treatment en_US
dc.description.sponsorship This study was supported by grants PI07/0577, PI08/1849 and PI10/1972 from Fondo de Investigaciones Sanitarias, Ministerio de Ciencia e Innovación, Spain and PI10-045, and from the Fundación Sociosanitaria de Castilla-La Mancha, Spain en_US
dc.format.extent 15 pag. es_ES
dc.format.mimetype application/pdf en
dc.language.iso eng en
dc.publisher Spandidos Publications en_US
dc.relation.ispartof International Journal of Oncology en_US
dc.subject.other Androgen en_US
dc.subject.other MET en_US
dc.subject.other Microarrays en_US
dc.subject.other Neurofibromin 2 en_US
dc.subject.other NF2 en_US
dc.subject.other Osteopontin SPP1 en_US
dc.subject.other Schwannoma en_US
dc.title Microarray analysis of gene expression in vestibular schwannomas reveals SPP1/MET signaling pathway and androgen receptor deregulation en_US
dc.type article en
dc.subject.eciencia Medicina es_ES
dc.identifier.doi 10.3892/ijo.2013.1798 es_ES
dc.identifier.publicationfirstpage 848 es_ES
dc.identifier.publicationissue 3 es_ES
dc.identifier.publicationlastpage 862 es_ES
dc.identifier.publicationvolume 42 es_ES
dc.type.version info:eu-repo/semantics/publishedVersion en
dc.rights.accessRights openAccess en
dc.authorUAM Lassaletta Garbayo, Luis (260274)
dc.authorUAM De Campos Gutiérrez, José María (261884)
dc.authorUAM Gavilán Bouzas, Javier (259836)

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