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dc.contributor.authorZagorac, Ivana 
dc.contributor.authorFernandez-Gaitero, Sara
dc.contributor.authorPenning, Renske
dc.contributor.authorPost, Harm
dc.contributor.authorBueno Verdejo, Maria Jose 
dc.contributor.authorMouron, Silvana Andrea 
dc.contributor.authorManso, Luis
dc.contributor.authorMorente Gallego, Manuel M 
dc.contributor.authorAlonso, Soledad
dc.contributor.authorSerra, Violeta
dc.contributor.authorMuñoz Peralta, Javier 
dc.contributor.authorGomez Lopez, Gonzalo 
dc.contributor.authorLopez-Acosta, Jose Francisco
dc.contributor.authorJimenez-Renard, Veronica
dc.contributor.authorGris-Oliver, Albert
dc.contributor.authorAl-Shahrour , Fatima 
dc.contributor.authorPiñeiro-Yañez, Elena
dc.contributor.authorMontoya-Suarez, Jose Luis
dc.contributor.authorApala, Juan V
dc.contributor.authorMoreno-Torres, Amalia
dc.contributor.authorColomer, Ramon
dc.contributor.authorDopazo, Ana 
dc.contributor.authorHeck, Albert J R
dc.contributor.authorAltelaar, Maarten
dc.contributor.authorQuintela Fandino, Miguel Angel 
dc.date.accessioned2018-10-25T10:22:43Z
dc.date.available2018-10-25T10:22:43Z
dc.date.issued2018-08-29
dc.identifier.citationNat Commun. 2018; 9(1): 3501.es_ES
dc.identifier.issn2041-1723es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/6527
dc.description.abstractTriple-negative breast cancer (TNBC) lacks prognostic and predictive markers. Here, we use high-throughput phosphoproteomics to build a functional TNBC taxonomy. A cluster of 159 phosphosites is upregulated in relapsed cases of a training set (n = 34 patients), with 11 hyperactive kinases accounting for this phosphoprofile. A mass-spectrometry-to-immunohistochemistry translation step, assessing 2 independent validation sets, reveals 6 kinases with preserved independent prognostic value. The kinases split the validation set into two patterns: one without hyperactive kinases being associated with a >90% relapse-free rate, and the other one showing ≥1 hyperactive kinase and being associated with an up to 9.5-fold higher relapse risk. Each kinase pattern encompasses different mutational patterns, simplifying mutation-based taxonomy. Drug regimens designed based on these 6 kinases show promising antitumour activity in TNBC cell lines and patient-derived xenografts. In summary, the present study elucidates phosphosites and kinases implicated in TNBC and suggests a target-based clinical classification system for TNBC.es_ES
dc.description.sponsorshipWe are grateful to the Spanish Biobanks integrated within the Spanish Network of National Biobanks for the tumor samples used in our investigations and to the Breast Cancer Group at VHIO for providing study materials. The present study was funded by FIS PI10/00288, FIS PI13/00430, and AECC Scientific Foundation “Beca de Retorno 2010”awarded to MQF; FIS PI11-00832, FIS PI14-00726, and ISCIII PIE15/00068 awarded to RC. I.Z. is a recipient of a La Caixa PhD Fellowship, 2011. S.F. is a recipient of a FPI grant (SEV-2015-0510-16-6). V.S. is supported by the Miguel Servet Program (CP14/00228). This work was also supported by the PRIME-XS project, Grant Agree- ment Number 262067, funded by the European Union Seventh Framework Program and the project Proteins At Work (project 184.032.201), a program of the Netherlands Proteomics Centre financed by the Netherlands Organisation for Scientific Research (NWO). M.A. kindly acknowledges NWO for financial support through a VIDI grant(723.012.102). CRIS Cancer Foundation contributed to this study with a generous donationes_ES
dc.language.isoenges_ES
dc.publisherNature Publishing Groupes_ES
dc.relation.isversionofPublisher's versiones_ES
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/*
dc.subjectSET ENRICHMENT ANALYSISes_ES
dc.subjectC-KITes_ES
dc.subjectPEPTIDE IDENTIFICATIONes_ES
dc.subjectTHERAPEUTIC TARGETSes_ES
dc.subjectSOMATIC MUTATIONSes_ES
dc.subjectTUMOR XENOGRAFTSes_ES
dc.subjectINHIBITIONes_ES
dc.subjectEXPRESSIONes_ES
dc.subjectLANDSCAPEes_ES
dc.titleIn vivo phosphoproteomics reveals kinase activity profiles that predict treatment outcome in triple-negative breast canceres_ES
dc.typeArtículoes_ES
dc.rights.licenseAtribución 4.0 Internacional*
dc.identifier.pubmedID30158526es_ES
dc.format.volume9es_ES
dc.format.number1es_ES
dc.format.page3501es_ES
dc.identifier.doi10.1038/s41467-018-05742-zes_ES
dc.contributor.funderAsociación Española Contra el Canceres_ES
dc.contributor.funderFundación La Caixaes_ES
dc.contributor.funderInstituto de Salud Carlos III - ISCIIIes_ES
dc.contributor.funderEuropean Commision
dc.contributor.funderNetherlands Organisation for Scientific Research
dc.contributor.funderCRIS Cancer Foundation (UK)
dc.description.peerreviewed
dc.identifier.e-issn2041-1723es_ES
dc.relation.publisherversionhttps://doi.org/10.1038/s41467-018-05742-zes_ES
dc.identifier.journalNature communicationses_ES
dc.repisalud.orgCNICCNIC::Unidades técnicas::Genómica
dc.repisalud.institucionCNIOes_ES
dc.repisalud.institucionCNIC
dc.repisalud.orgCNIOCNIO::Grupos de investigaciónes_ES
dc.repisalud.orgCNIOCNIO::Unidades técnicas::Unidad de Investigación Clínica de Cáncer de Mamaes_ES
dc.relation.projectIDinfo:eu-repo/grantAgreement/EC/FP7/262067es_ES
dc.rights.accessRightsinfo:eu-repo/semantics/openAccesses_ES


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