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dc.contributor.authorKrzemiński, Patryk-
dc.contributor.authorCorchete, Luis A.-
dc.contributor.authorGarcía, Juan L.-
dc.contributor.authorLópez-Corral, L.-
dc.contributor.authorFermiñán, Encarnación-
dc.contributor.authorGarcía García, Eva María-
dc.contributor.authorMartín, Ana-África-
dc.contributor.authorHernández, Jesús M.-
dc.contributor.authorGarcía-Sanz, Ramón-
dc.contributor.authorSan Miguel, Jesús F.-
dc.contributor.authorGutiérrez, Norma Carmen-
dc.date.accessioned2018-08-10T11:12:35Z-
dc.date.available2018-08-10T11:12:35Z-
dc.date.issued2016-
dc.identifierdoi: 10.18632/oncotarget.13025-
dc.identifiere-issn: 1949-2553-
dc.identifier.citationOncotarget 7(49): 80664-80679 (2016)-
dc.identifier.urihttp://hdl.handle.net/10261/168573-
dc.description.abstractMultiple myeloma (MM) remains incurable despite the introduction of novel agents, and a relapsing course is observed in most patients. Although the development of genomic technologies has greatly improved our understanding of MM pathogenesis, the mechanisms underlying relapse have been less thoroughly investigated. In this study, an integrative analysis of DNA copy number, DNA methylation and gene expression was conducted in matched diagnosis and relapse samples from MM patients. Overall, the acquisition of abnormalities at relapse was much more frequent than the loss of lesions present at diagnosis, and DNA losses were significantly more frequent in relapse than in diagnosis samples. Interestingly, copy number abnormalities involving more than 100 Mb of DNA at relapse significantly affect the gene expression of these samples, provoking a particular deregulation of the IL-8 pathway. On the other hand, no significant modifications of gene expression were observed in those samples with less than 100 Mb affected by chromosomal changes. Although several statistical approaches were used to identify genes whose abnormal expression at relapse was regulated by methylation, only two genes that were significantly deregulated in relapse samples (SORL1 and GLT1D1) showed a negative correlation between methylation and expression. Further analysis revealed that DNA methylation was involved in regulating SORL1 expression in MM. Finally, relevant changes in gene expression observed in relapse samples, such us downregulation of CD27 and P2RY8, were most likely not preceded by alterations in the corresponding DNA. Taken together, these results suggest that the genomic heterogeneity described at diagnosis remains at relapse.-
dc.description.sponsorshipThis work was partially supported by the Instituto de Salud Carlos III-Cofinanciación con fondos FEDER (PI080568, PS0901897 and PI13/00111), the Gerencia Regional de Salud, Junta de Castilla y León (GRS202/A08 and GRS 702/A/11), the Spanish Myeloma Network Program (RD06/0020/0006) and the Asociación Española Contra el Cáncer (AECC, GCB120981SAN).-
dc.publisherImpact Journals-
dc.relation.isversionofPublisher's version-
dc.rightsopenAccess-
dc.subjectDNA methylation-
dc.subjectMicroarrays-
dc.subjectMultiple myeloma-
dc.subjectSORL1-
dc.subjectSNP-
dc.titleIntegrative analysis of DNA copy number, DNA methylation and gene expression in multiple myeloma reveals alterations related to relapse-
dc.typeartículo-
dc.identifier.doi10.18632/oncotarget.13025-
dc.relation.publisherversionhttps://doi.org/10.18632/oncotarget.13025-
dc.date.updated2018-08-10T11:12:36Z-
dc.description.versionPeer Reviewed-
dc.language.rfc3066eng-
dc.rights.licensehttp://creativecommons.org/licenses/by/3.0/-
dc.contributor.funderAsociación Española Contra el Cáncer-
dc.contributor.funderInstituto de Salud Carlos III-
dc.contributor.funderJunta de Castilla y León-
dc.contributor.funderEuropean Commission-
dc.contributor.funderGrupo Español de Mieloma-
dc.relation.csic-
dc.identifier.funderhttp://dx.doi.org/10.13039/501100000780es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100004587es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/501100014180es_ES
dc.identifier.pmid27811368-
dc.type.coarhttp://purl.org/coar/resource_type/c_6501es_ES
item.openairetypeartículo-
item.cerifentitytypePublications-
item.grantfulltextopen-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.fulltextWith Fulltext-
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