Pan-cancer association of a centrosome amplification gene expression signature with genomic alterations and clinical outcome
Autor(a) principal: | |
---|---|
Data de Publicação: | 2019 |
Outros Autores: | , , , |
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. |
id |
RCAP_e8af95975ed32d4c3af91783f145a17b |
---|---|
oai_identifier_str |
oai:repositorio-aberto.up.pt:10216/136305 |
network_acronym_str |
RCAP |
network_name_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository_id_str |
7160 |
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 |
format |
article |
status_str |
publishedVersion |
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 |
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 |
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) 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 |
instacron_str |
RCAAP |
institution |
RCAAP |
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 |
repository.mail.fl_str_mv |
|
_version_ |
1799136068830756865 |