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Pan-cancer association of a centrosome amplification gene expression signature with genomic alterations and clinical outcome

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dc.contributor.authorAlmeida, Bernardo P. De
dc.contributor.authorVieira, André F.
dc.contributor.authorParedes, Joana
dc.contributor.authorBettencourt-Dias, Mónica
dc.contributor.authorBarbosa-Morais, Nuno
dc.date.accessioned2021-12-10T14:56:24Z
dc.date.available2021-12-10T14:56:24Z
dc.date.issued2019
dc.descriptionCopyright: © 2019 de Almeida et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.pt_PT
dc.description.abstractCentrosome amplification (CA) is a common feature of human tumours and a promising target for cancer therapy. However, CA's pan-cancer prevalence, molecular role in tumourigenesis and therapeutic value in the clinical setting are still largely unexplored. Here, we used a transcriptomic signature (CA20) to characterise the landscape of CA-associated gene expression in 9,721 tumours from The Cancer Genome Atlas (TCGA). CA20 is upregulated in cancer and associated with distinct clinical and molecular features of breast cancer, consistently with our experimental CA quantification in patient samples. Moreover, we show that CA20 upregulation is positively associated with genomic instability, alteration of specific chromosomal arms and C>T mutations, and we propose novel molecular players associated with CA in cancer. Finally, high CA20 is associated with poor prognosis and, by integrating drug sensitivity with drug perturbation profiles in cell lines, we identify candidate compounds for selectively targeting cancer cells exhibiting transcriptomic evidence for CA.pt_PT
dc.description.sponsorshipThis work was funded by UID/BIM/50005/2019, project funded by Fundação para a Ciência e a Tecnologia (FCT) / Ministério da Ciência, Tecnologia e Ensino Superior (MCTES) (https://www.fct.pt/index.phtml.en) through Fundos do Orçamento de Estado. A.F.V. is a FCT fellow (SFRH/BPD/90303/2012). The M.B-D. laboratory is supported by IGC (http://www.igc.gulbenkian.pt/), an EMBO Installation grant (http://embo.org/funding-awards/installation-grants), ERC grant ERC-2010-StG-261344 (https://erc.europa.eu/funding/starting-grants), FCT grants (Investigador FCT to M.B-D., POCI-01-0145-FEDER-016390 and PTDC/BIM-ONC/6858/2014) and a FCT-Harvard Medical School Program Portugal grant (HMSP-CT/SAU-ICT/0075/2009) (https://postgraduateeducation.hms.harvard.edu/). N.L.B-M. is supported by an EMBO Installation Grant (3057) and an Investigador FCT Starting Grant (IF/00595/2014).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationPLoS Comput Biol 15(3): e1006832pt_PT
dc.identifier.doi10.1371/journal.pcbi.1006832pt_PT
dc.identifier.eissn1553-7358
dc.identifier.issn1553-734X
dc.identifier.urihttp://hdl.handle.net/10451/50338
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherPLOSpt_PT
dc.relationERC-2010-StG-261344pt_PT
dc.relationInstituto de Medicina Molecular
dc.relationP-CADHERIN AS A REGULATOR OF EPITHELIAL CELL POLARITY AND STEM CELL DIVISION AND THE SIGNIFICANCE OF ITS OVEREXPRESSION IN BRCA1-ASSOCIATED BASAL-LIKE BREAST CARCINOMAS
dc.relationIF/00595/2014pt_PT
dc.relation"Length matters: Causes and consequences of centriole length deregulation in cancer"
dc.relation.publisherversionhttps://journals.plos.org/ploscompbiol/pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.titlePan-cancer association of a centrosome amplification gene expression signature with genomic alterations and clinical outcomept_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardNumberUID/BIM/50005/2019
oaire.awardNumberSFRH/BPD/90303/2012
oaire.awardNumberPTDC/BIM-ONC/6858/2014
oaire.awardNumberHMSP-CT/SAU-ICT/0075/2009
oaire.awardTitleInstituto de Medicina Molecular
oaire.awardTitleP-CADHERIN AS A REGULATOR OF EPITHELIAL CELL POLARITY AND STEM CELL DIVISION AND THE SIGNIFICANCE OF ITS OVEREXPRESSION IN BRCA1-ASSOCIATED BASAL-LIKE BREAST CARCINOMAS
oaire.awardTitle"Length matters: Causes and consequences of centriole length deregulation in cancer"
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/6817 - DCRRNI ID/UID%2FBIM%2F50005%2F2019/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBPD%2F90303%2F2012/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FBIM-ONC%2F6858%2F2014/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/HMSP-CT%2FSAU-ICT%2F0075%2F2009/PT
oaire.citation.issue3pt_PT
oaire.citation.startPagee1006832pt_PT
oaire.citation.titlePLOS Computational Biologypt_PT
oaire.citation.volume15pt_PT
oaire.fundingStream6817 - DCRRNI ID
oaire.fundingStream3599-PPCDT
oaire.fundingStream3599-PPCDT
person.familyNameAlmeida
person.familyNameBARBOSA MORAIS
person.givenNameBernardo
person.givenNameNUNO LUÍS
person.identifierI-2743-2013
person.identifier.ciencia-id5C19-CA77-A74D
person.identifier.orcid0000-0002-6084-6775
person.identifier.orcid0000-0002-1215-0538
person.identifier.scopus-author-id6507555084
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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