Genomic and transcriptomic characterization of the human glioblastoma cell line AHOL1

Detalhes bibliográficos
Autor(a) principal: Ferreira, Wallax Augusto Silva
Data de Publicação: 2021
Outros Autores: Amorim, Carolina Koury Nassar, Burbano, Rommel R, Villacis, Rebeca A. R, Marchi, Fabio Albuquerque, Medina, T. S, Lima, M. M. C. de, Oliveira, Edivaldo Herculano Corrêa de
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Digital do Instituto Evandro Chagas (Patuá)
Texto Completo: https://patua.iec.gov.br/handle/iec/4244
Resumo: Cancer cell lines are widely used as in vitro models of tumorigenesis, facilitating fundamental discoveries in cancer biology and translational medicine. Currently, there are few options for glioblastoma (GBM) treatment and limited in vitro models with accurate genomic and transcriptomic characterization. Here, a detailed characterization of a new GBM cell line, namely AHOL1, was conducted in order to fully characterize its molecular composition based on its karyotype, copy number alteration (CNA), and transcriptome profiling, followed by the validation of key elements associated with GBM tumorigenesis. Large numbers of CNAs and differentially expressed genes (DEGs) were identified. CNAs were distributed throughout the genome, including gains at Xq11.1-q28, Xp22.33-p11.1, Xq21.1-q21.33, 4p15.1-p14, 8q23.2-q23.3 and losses at Yq11.21-q12, Yp11.31-p11.2, and 15q11.1-q11.2 positions. Nine druggable genes were identified, including HCRTR2, ETV1, PTPRD, PRKX, STS, RPS6KA6, ZFY, USP9Y, and KDM5D. By integrating DEGs and CNAs, we identified 57 overlapping genes enriched in fourteen pathways. Altered expression of several cancer-related candidates found in the DEGs-CNA dataset was confirmed by RT-qPCR. Taken together, this first comprehensive genomic and transcriptomic landscape of AHOL1 provides unique resources for further studies and identifies several druggable targets that may be useful for therapeutics and biologic and molecular investigation of GBM.
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spelling Ferreira, Wallax Augusto SilvaAmorim, Carolina Koury NassarBurbano, Rommel RVillacis, Rebeca A. RMarchi, Fabio AlbuquerqueMedina, T. SLima, M. M. C. deOliveira, Edivaldo Herculano Corrêa de2021-02-03T23:22:18Z2021-02-03T23:22:18Z2021FERREIRA, Wallax Augusto Silva et al. Genomic and transcriptomic characterization of the human glioblastoma cell line AHOL1. Brazilian Journal of Medical and Biological Research, v. 54, n. 3, p. 1-12, Jan. 2021.1414-431Xhttps://patua.iec.gov.br/handle/iec/424410.1590/1414-431x20209571Cancer cell lines are widely used as in vitro models of tumorigenesis, facilitating fundamental discoveries in cancer biology and translational medicine. Currently, there are few options for glioblastoma (GBM) treatment and limited in vitro models with accurate genomic and transcriptomic characterization. Here, a detailed characterization of a new GBM cell line, namely AHOL1, was conducted in order to fully characterize its molecular composition based on its karyotype, copy number alteration (CNA), and transcriptome profiling, followed by the validation of key elements associated with GBM tumorigenesis. Large numbers of CNAs and differentially expressed genes (DEGs) were identified. CNAs were distributed throughout the genome, including gains at Xq11.1-q28, Xp22.33-p11.1, Xq21.1-q21.33, 4p15.1-p14, 8q23.2-q23.3 and losses at Yq11.21-q12, Yp11.31-p11.2, and 15q11.1-q11.2 positions. Nine druggable genes were identified, including HCRTR2, ETV1, PTPRD, PRKX, STS, RPS6KA6, ZFY, USP9Y, and KDM5D. By integrating DEGs and CNAs, we identified 57 overlapping genes enriched in fourteen pathways. Altered expression of several cancer-related candidates found in the DEGs-CNA dataset was confirmed by RT-qPCR. Taken together, this first comprehensive genomic and transcriptomic landscape of AHOL1 provides unique resources for further studies and identifies several druggable targets that may be useful for therapeutics and biologic and molecular investigation of GBM.This research was funded by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) (Grant Number: 455078/2014-9) and Evandro Chagas Institute.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de Cultura de Tecidos e Citogenética. Ananindeua, PA, BrasilMinistério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de Cultura de Tecidos e Citogenética. Ananindeua, PA, BrasilUniversidade Federal do Pará. Instituto de Ciências Biológicas. Laboratório de Citogenética Humana. Belém, PA, Brasil / Hospital Universitário João de Barros Barreto. Núcleo de Pesquisas em Oncologia. Belém, PA, Brasil / Hospital Ophir Loyola. Laboratório de Biologia Molecular. Belém, PA, Brasil.Universidade de Brasília. Instituto de Ciências Biológicas. Departamento de Genética e Morfologia. Brasília, DF, Brasil.A.C. Camargo Cancer Center. Centro Internacional de Pesquisa. São Paulo, SP, Brasil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Faculdade de Biomedicina. Belém, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde. Instituto Evandro Chagas. Laboratório de Cultura de Tecidos e Citogenética. Ananindeua, PA, Brasil / Universidade Federal do Pará. Instituto de Ciências Exatas e Naturais. Faculdade de Ciências Naturais. Belém, PA, Brasil.engAssociação Brasileira de Divulgação CientíficaGenomic and transcriptomic characterization of the human glioblastoma cell line AHOL1info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleNeoplasias EncefálicasGlioblastoma / genéticaGliomaHibridização Genômica Comparativa / métodosinfo:eu-repo/semantics/openAccessreponame:Repositório Digital do Instituto Evandro Chagas (Patuá)instname:Instituto Evandro Chagas (IEC)instacron:IECORIGINALGenomic and transcriptomic characterization of the human glioblastoma cell line AHOL1.pdfGenomic and transcriptomic characterization of the human glioblastoma cell line AHOL1.pdfapplication/pdf819645https://patua.iec.gov.br/bitstreams/73ca2cac-de34-4f4e-aa63-6f64ee5ec44c/download79ce88828466921a84f47f04968a41baMD51LICENSElicense.txtlicense.txttext/plain; charset=utf-82182https://patua.iec.gov.br/bitstreams/0494e0a7-91b9-428f-83ff-d06f4c560718/download11832eea31b16df8613079d742d61793MD52TEXTGenomic and transcriptomic characterization of the human glioblastoma cell line AHOL1.pdf.txtGenomic and transcriptomic characterization of the human glioblastoma cell line AHOL1.pdf.txtExtracted texttext/plain54988https://patua.iec.gov.br/bitstreams/a8da75c4-6f6e-4d14-a9da-ee9bccfaa7b5/downloadd6e0a70b8a46af6a3f586e3d3c7b73e0MD55THUMBNAILGenomic and transcriptomic characterization of the human glioblastoma cell line AHOL1.pdf.jpgGenomic and transcriptomic characterization of the human glioblastoma cell line AHOL1.pdf.jpgGenerated Thumbnailimage/jpeg5989https://patua.iec.gov.br/bitstreams/658c2eaf-eea4-4c37-9959-f071e132baa6/downloadbe4246b152c2248dc2edf653e08aed60MD56iec/42442023-05-16 19:10:18.224oai:patua.iec.gov.br:iec/4244https://patua.iec.gov.brRepositório InstitucionalPUBhttps://patua.iec.gov.br/oai/requestclariceneta@iec.gov.br || Biblioteca@iec.gov.bropendoar:2023-05-16T19:10:18Repositório Digital do Instituto Evandro Chagas (Patuá) - Instituto Evandro Chagas (IEC)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
dc.title.pt_BR.fl_str_mv Genomic and transcriptomic characterization of the human glioblastoma cell line AHOL1
title Genomic and transcriptomic characterization of the human glioblastoma cell line AHOL1
spellingShingle Genomic and transcriptomic characterization of the human glioblastoma cell line AHOL1
Ferreira, Wallax Augusto Silva
Neoplasias Encefálicas
Glioblastoma / genética
Glioma
Hibridização Genômica Comparativa / métodos
title_short Genomic and transcriptomic characterization of the human glioblastoma cell line AHOL1
title_full Genomic and transcriptomic characterization of the human glioblastoma cell line AHOL1
title_fullStr Genomic and transcriptomic characterization of the human glioblastoma cell line AHOL1
title_full_unstemmed Genomic and transcriptomic characterization of the human glioblastoma cell line AHOL1
title_sort Genomic and transcriptomic characterization of the human glioblastoma cell line AHOL1
author Ferreira, Wallax Augusto Silva
author_facet Ferreira, Wallax Augusto Silva
Amorim, Carolina Koury Nassar
Burbano, Rommel R
Villacis, Rebeca A. R
Marchi, Fabio Albuquerque
Medina, T. S
Lima, M. M. C. de
Oliveira, Edivaldo Herculano Corrêa de
author_role author
author2 Amorim, Carolina Koury Nassar
Burbano, Rommel R
Villacis, Rebeca A. R
Marchi, Fabio Albuquerque
Medina, T. S
Lima, M. M. C. de
Oliveira, Edivaldo Herculano Corrêa de
author2_role author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Ferreira, Wallax Augusto Silva
Amorim, Carolina Koury Nassar
Burbano, Rommel R
Villacis, Rebeca A. R
Marchi, Fabio Albuquerque
Medina, T. S
Lima, M. M. C. de
Oliveira, Edivaldo Herculano Corrêa de
dc.subject.decsPrimary.pt_BR.fl_str_mv Neoplasias Encefálicas
Glioblastoma / genética
Glioma
topic Neoplasias Encefálicas
Glioblastoma / genética
Glioma
Hibridização Genômica Comparativa / métodos
dc.subject.decsPrimary.pt-BR.fl_str_mv Hibridização Genômica Comparativa / métodos
description Cancer cell lines are widely used as in vitro models of tumorigenesis, facilitating fundamental discoveries in cancer biology and translational medicine. Currently, there are few options for glioblastoma (GBM) treatment and limited in vitro models with accurate genomic and transcriptomic characterization. Here, a detailed characterization of a new GBM cell line, namely AHOL1, was conducted in order to fully characterize its molecular composition based on its karyotype, copy number alteration (CNA), and transcriptome profiling, followed by the validation of key elements associated with GBM tumorigenesis. Large numbers of CNAs and differentially expressed genes (DEGs) were identified. CNAs were distributed throughout the genome, including gains at Xq11.1-q28, Xp22.33-p11.1, Xq21.1-q21.33, 4p15.1-p14, 8q23.2-q23.3 and losses at Yq11.21-q12, Yp11.31-p11.2, and 15q11.1-q11.2 positions. Nine druggable genes were identified, including HCRTR2, ETV1, PTPRD, PRKX, STS, RPS6KA6, ZFY, USP9Y, and KDM5D. By integrating DEGs and CNAs, we identified 57 overlapping genes enriched in fourteen pathways. Altered expression of several cancer-related candidates found in the DEGs-CNA dataset was confirmed by RT-qPCR. Taken together, this first comprehensive genomic and transcriptomic landscape of AHOL1 provides unique resources for further studies and identifies several druggable targets that may be useful for therapeutics and biologic and molecular investigation of GBM.
publishDate 2021
dc.date.accessioned.fl_str_mv 2021-02-03T23:22:18Z
dc.date.available.fl_str_mv 2021-02-03T23:22:18Z
dc.date.issued.fl_str_mv 2021
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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status_str publishedVersion
dc.identifier.citation.fl_str_mv FERREIRA, Wallax Augusto Silva et al. Genomic and transcriptomic characterization of the human glioblastoma cell line AHOL1. Brazilian Journal of Medical and Biological Research, v. 54, n. 3, p. 1-12, Jan. 2021.
dc.identifier.uri.fl_str_mv https://patua.iec.gov.br/handle/iec/4244
dc.identifier.issn.-.fl_str_mv 1414-431X
dc.identifier.doi.-.fl_str_mv 10.1590/1414-431x20209571
identifier_str_mv FERREIRA, Wallax Augusto Silva et al. Genomic and transcriptomic characterization of the human glioblastoma cell line AHOL1. Brazilian Journal of Medical and Biological Research, v. 54, n. 3, p. 1-12, Jan. 2021.
1414-431X
10.1590/1414-431x20209571
url https://patua.iec.gov.br/handle/iec/4244
dc.language.iso.fl_str_mv eng
language eng
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dc.publisher.none.fl_str_mv Associação Brasileira de Divulgação Científica
publisher.none.fl_str_mv Associação Brasileira de Divulgação Científica
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