Copy number profiling of Brazilian astrocytomas
Autor(a) principal: | |
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Data de Publicação: | 2016 |
Outros Autores: | , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/1822/45043 |
Resumo: | Copy number alterations (CNA) are one of the driving mechanisms of glioma tumorigenesis, and are currently used as important biomarkers in the routine setting. Therefore, we performed CNA profiling of 65 astrocytomas of distinct malignant grades (WHO grade I-IV) of Brazilian origin, using array-CGH and microsatellite instability analysis (MSI), and investigated their correlation with TERT and IDH1 mutational status and clinico-pathological features. Furthermore, in silico analysis using the Oncomine database was performed to validate our findings and extend the findings to gene expression level. We found that the number of genomic alterations increases in accordance with glioma grade. In glioblastomas (GBM), the most common alterations were gene amplifications (PDGFRA, KIT, KDR, EGFR, and MET) and deletions (CDKN2A and PTEN). Log-rank analysis correlated EGFR amplification and/or chr7 gain with better survival of the patients. MSI was observed in 11% of GBMs. A total of 69% of GBMs presented TERT mutation, whereas IDH1 mutation was most frequent in diffuse (85.7%) and anaplastic (100%) astrocytomas. The combination of 1p19q deletion and TERT and IDH1 mutational status separated tumor groups that showed distinct age of diagnosis and outcome. In silico validation pointed to less explored genes that may be worthy of future investigation, such as CDK2, DMRTA1, and MTAP. Herein, using an extensive integrated analysis, we indicated potentially important genes, not extensively studied in gliomas, that could be further explored to assess their biological and clinical impact in astrocytomas. |
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Copy number profiling of Brazilian astrocytomasGenomicsGlioblastomasGliomasTERTIDH1Science & TechnologyCopy number alterations (CNA) are one of the driving mechanisms of glioma tumorigenesis, and are currently used as important biomarkers in the routine setting. Therefore, we performed CNA profiling of 65 astrocytomas of distinct malignant grades (WHO grade I-IV) of Brazilian origin, using array-CGH and microsatellite instability analysis (MSI), and investigated their correlation with TERT and IDH1 mutational status and clinico-pathological features. Furthermore, in silico analysis using the Oncomine database was performed to validate our findings and extend the findings to gene expression level. We found that the number of genomic alterations increases in accordance with glioma grade. In glioblastomas (GBM), the most common alterations were gene amplifications (PDGFRA, KIT, KDR, EGFR, and MET) and deletions (CDKN2A and PTEN). Log-rank analysis correlated EGFR amplification and/or chr7 gain with better survival of the patients. MSI was observed in 11% of GBMs. A total of 69% of GBMs presented TERT mutation, whereas IDH1 mutation was most frequent in diffuse (85.7%) and anaplastic (100%) astrocytomas. The combination of 1p19q deletion and TERT and IDH1 mutational status separated tumor groups that showed distinct age of diagnosis and outcome. In silico validation pointed to less explored genes that may be worthy of future investigation, such as CDK2, DMRTA1, and MTAP. Herein, using an extensive integrated analysis, we indicated potentially important genes, not extensively studied in gliomas, that could be further explored to assess their biological and clinical impact in astrocytomas.This study was partially supported by the Universal/National Counsel of Technological and Scientific Development (CNPq) (475358/2011-2 – R.M.R.), São Paulo Research Foundation (FAPESP) (2012/19590-0 and 2016/09105-8 – R.M.R.) and the Fundação para a Ciência e a Tecnologia (FCT) (PTDC/SAU-ONC/115513/2009-FCMO-01-0124FEDER-015949). L.T.B. was recipient of FAPESP fellowships (2011/ 08523-7 and 2012/08287-4), N.C.C.was recipient of a FAPESP fellowship (2013/25787-3), M.L.S. was recipient of a CNPq/Programa Institucional de Bolsas de Iniciação Científica (PIBIC) fellowship (100707/ 2014-9), W.M. was recipient of FAPESP (2013/15515-6) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)/ Programa de Suporte à Pós-Graduação de Instituições de Ensino Particulares (Prosup) fellowships, and M.V.P. was a Postdoctoral research fellow under the FCT project PTDC/SAU-ONC/115513/2009. R.M.R. has a CNPq scholarship. C.J. and A.M. acknowledge National Health Service funding to the National Institute for Health Research Biomedical Research Centre at The Royal Marsden and the Institute of Cancer Research.info:eu-repo/semantics/publishedVersionGenetics Society of America[et.al.]Universidade do MinhoBidinotto, Lucas TadeuTorrieri, RaulMackay, AlanAlmeida, Gisele CaravinaPereira, Marta VianaCarloni, Adriana C.Spina, Maria LuisaCampanella, Nathália C.Menezes, Weder P.Reis, R. M.2016-07-062016-07-06T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/45043engBidinotto, L. T., Torrieri, R., Mackay, A., Almeida, G. C., Viana-Pereira, M., Cruvinel-Carloni, A., . . . Reis, R. M. (2016). Copy number profiling of Brazilian astrocytomas. G3: Genes, Genomes, Genetics, 6(7), 1867-1878. doi: 10.1534/g3.116.0298842160-18362160-183610.1534/g3.116.02988427172220http://www.g3journal.org/content/6/7/1867.longinfo: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:RCAAP2023-07-21T12:34:46Zoai:repositorium.sdum.uminho.pt:1822/45043Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:30:30.987024Repositório 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 |
Copy number profiling of Brazilian astrocytomas |
title |
Copy number profiling of Brazilian astrocytomas |
spellingShingle |
Copy number profiling of Brazilian astrocytomas Bidinotto, Lucas Tadeu Genomics Glioblastomas Gliomas TERT IDH1 Science & Technology |
title_short |
Copy number profiling of Brazilian astrocytomas |
title_full |
Copy number profiling of Brazilian astrocytomas |
title_fullStr |
Copy number profiling of Brazilian astrocytomas |
title_full_unstemmed |
Copy number profiling of Brazilian astrocytomas |
title_sort |
Copy number profiling of Brazilian astrocytomas |
author |
Bidinotto, Lucas Tadeu |
author_facet |
Bidinotto, Lucas Tadeu Torrieri, Raul Mackay, Alan Almeida, Gisele Caravina Pereira, Marta Viana Carloni, Adriana C. Spina, Maria Luisa Campanella, Nathália C. Menezes, Weder P. Reis, R. M. |
author_role |
author |
author2 |
Torrieri, Raul Mackay, Alan Almeida, Gisele Caravina Pereira, Marta Viana Carloni, Adriana C. Spina, Maria Luisa Campanella, Nathália C. Menezes, Weder P. Reis, R. M. |
author2_role |
author author author author author author author author author |
dc.contributor.none.fl_str_mv |
[et.al.] Universidade do Minho |
dc.contributor.author.fl_str_mv |
Bidinotto, Lucas Tadeu Torrieri, Raul Mackay, Alan Almeida, Gisele Caravina Pereira, Marta Viana Carloni, Adriana C. Spina, Maria Luisa Campanella, Nathália C. Menezes, Weder P. Reis, R. M. |
dc.subject.por.fl_str_mv |
Genomics Glioblastomas Gliomas TERT IDH1 Science & Technology |
topic |
Genomics Glioblastomas Gliomas TERT IDH1 Science & Technology |
description |
Copy number alterations (CNA) are one of the driving mechanisms of glioma tumorigenesis, and are currently used as important biomarkers in the routine setting. Therefore, we performed CNA profiling of 65 astrocytomas of distinct malignant grades (WHO grade I-IV) of Brazilian origin, using array-CGH and microsatellite instability analysis (MSI), and investigated their correlation with TERT and IDH1 mutational status and clinico-pathological features. Furthermore, in silico analysis using the Oncomine database was performed to validate our findings and extend the findings to gene expression level. We found that the number of genomic alterations increases in accordance with glioma grade. In glioblastomas (GBM), the most common alterations were gene amplifications (PDGFRA, KIT, KDR, EGFR, and MET) and deletions (CDKN2A and PTEN). Log-rank analysis correlated EGFR amplification and/or chr7 gain with better survival of the patients. MSI was observed in 11% of GBMs. A total of 69% of GBMs presented TERT mutation, whereas IDH1 mutation was most frequent in diffuse (85.7%) and anaplastic (100%) astrocytomas. The combination of 1p19q deletion and TERT and IDH1 mutational status separated tumor groups that showed distinct age of diagnosis and outcome. In silico validation pointed to less explored genes that may be worthy of future investigation, such as CDK2, DMRTA1, and MTAP. Herein, using an extensive integrated analysis, we indicated potentially important genes, not extensively studied in gliomas, that could be further explored to assess their biological and clinical impact in astrocytomas. |
publishDate |
2016 |
dc.date.none.fl_str_mv |
2016-07-06 2016-07-06T00:00:00Z |
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 |
http://hdl.handle.net/1822/45043 |
url |
http://hdl.handle.net/1822/45043 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Bidinotto, L. T., Torrieri, R., Mackay, A., Almeida, G. C., Viana-Pereira, M., Cruvinel-Carloni, A., . . . Reis, R. M. (2016). Copy number profiling of Brazilian astrocytomas. G3: Genes, Genomes, Genetics, 6(7), 1867-1878. doi: 10.1534/g3.116.029884 2160-1836 2160-1836 10.1534/g3.116.029884 27172220 http://www.g3journal.org/content/6/7/1867.long |
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 |
Genetics Society of America |
publisher.none.fl_str_mv |
Genetics Society of America |
dc.source.none.fl_str_mv |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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