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

Detalhes bibliográficos
Autor(a) principal: Almeida, Bernardo P. De
Data de Publicação: 2019
Outros Autores: Vieira, André F., Paredes, Joana, Bettencourt-Dias, Mónica, Barbosa-Morais, Nuno
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10451/50338
Resumo: Copyright: © 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.
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spelling Pan-cancer association of a centrosome amplification gene expression signature with genomic alterations and clinical outcomeCopyright: © 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.Centrosome 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.This 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).PLOSRepositório da Universidade de LisboaAlmeida, Bernardo P. DeVieira, André F.Paredes, JoanaBettencourt-Dias, MónicaBarbosa-Morais, Nuno2021-12-10T14:56:24Z20192019-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/50338engPLoS Comput Biol 15(3): e10068321553-734X10.1371/journal.pcbi.10068321553-7358info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T16:54:31Zoai:repositorio.ul.pt:10451/50338Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:01:51.226671Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Pan-cancer association of a centrosome amplification gene expression signature with genomic alterations and clinical outcome
title Pan-cancer association of a centrosome amplification gene expression signature with genomic alterations and clinical outcome
spellingShingle Pan-cancer association of a centrosome amplification gene expression signature with genomic alterations and clinical outcome
Almeida, Bernardo P. De
title_short Pan-cancer association of a centrosome amplification gene expression signature with genomic alterations and clinical outcome
title_full Pan-cancer association of a centrosome amplification gene expression signature with genomic alterations and clinical outcome
title_fullStr Pan-cancer association of a centrosome amplification gene expression signature with genomic alterations and clinical outcome
title_full_unstemmed Pan-cancer association of a centrosome amplification gene expression signature with genomic alterations and clinical outcome
title_sort Pan-cancer association of a centrosome amplification gene expression signature with genomic alterations and clinical outcome
author Almeida, Bernardo P. De
author_facet Almeida, Bernardo P. De
Vieira, André F.
Paredes, Joana
Bettencourt-Dias, Mónica
Barbosa-Morais, Nuno
author_role author
author2 Vieira, André F.
Paredes, Joana
Bettencourt-Dias, Mónica
Barbosa-Morais, Nuno
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Repositório da Universidade de Lisboa
dc.contributor.author.fl_str_mv Almeida, Bernardo P. De
Vieira, André F.
Paredes, Joana
Bettencourt-Dias, Mónica
Barbosa-Morais, Nuno
description Copyright: © 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.
publishDate 2019
dc.date.none.fl_str_mv 2019
2019-01-01T00:00:00Z
2021-12-10T14:56:24Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10451/50338
url http://hdl.handle.net/10451/50338
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv PLoS Comput Biol 15(3): e1006832
1553-734X
10.1371/journal.pcbi.1006832
1553-7358
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv PLOS
publisher.none.fl_str_mv PLOS
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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