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

Detalhes bibliográficos
Autor(a) principal: Almeida, B
Data de Publicação: 2019
Outros Autores: Vieira, AF, Paredes, J, Bettencourt-Dias, M, Barbosa-Morais, N
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: https://hdl.handle.net/10216/136305
Resumo: 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.
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spelling Pan-cancer association of a centrosome amplification gene expression signature with genomic alterations and clinical outcomeCentrosome 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.Public Library of Science20192019-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10216/136305eng1553-734X10.1371/journal.pcbi.1006832Almeida, BVieira, AFParedes, JBettencourt-Dias, MBarbosa-Morais, Ninfo: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:RCAAP2023-11-29T15:03:52Zoai:repositorio-aberto.up.pt:10216/136305Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T00:14:48.047264Repositório 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, B
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, B
author_facet Almeida, B
Vieira, AF
Paredes, J
Bettencourt-Dias, M
Barbosa-Morais, N
author_role author
author2 Vieira, AF
Paredes, J
Bettencourt-Dias, M
Barbosa-Morais, N
author2_role author
author
author
author
dc.contributor.author.fl_str_mv Almeida, B
Vieira, AF
Paredes, J
Bettencourt-Dias, M
Barbosa-Morais, N
description 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.
publishDate 2019
dc.date.none.fl_str_mv 2019
2019-01-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
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dc.identifier.uri.fl_str_mv https://hdl.handle.net/10216/136305
url https://hdl.handle.net/10216/136305
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 1553-734X
10.1371/journal.pcbi.1006832
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dc.publisher.none.fl_str_mv Public Library of Science
publisher.none.fl_str_mv Public Library of Science
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
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