Prognostic stratification of adult primary glioblastoma multiforme patients based on their tumor gene amplification profiles
Autor(a) principal: | |
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Data de Publicação: | 2018 |
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/10316/107797 https://doi.org/10.18632/oncotarget.25562 |
Resumo: | Several classification systems have been proposed to address genomic heterogeneity of glioblastoma multiforme, but they either showed limited prognostic value and/or are difficult to implement in routine diagnostics. Here we propose a prognostic stratification model for these primary tumors based on tumor gene amplification profiles, that might be easily implemented in routine diagnostics, and potentially improve the patients management. Gene amplification profiles were prospectively evaluated in 80 primary glioblastoma multiforme tumors using single-nucleotide polymorphism arrays and the results obtained validated in publicly available data from 267/347 cases. Gene amplification was detected in 45% of patients, and chromosome 7p11.2 including the EGFR gene, was the most frequently amplified chromosomal region - either alone (18%) or in combination with amplification of DNA sequences in other chromosomal regions (10% of cases). Other frequently amplified DNA sequences included regions in chromosomes 12q(10%), 4q12(7%) and 1q32.1(4%). Based on their gene amplification profiles, glioblastomas were subdivided into: i) tumors with no gene amplification (55%); ii) tumors with chromosome 7p/EGFR gene amplification (with or without amplification of other chromosomal regions) (38%); and iii) glioblastoma multiforme with a single (11%) or multiple (6%) amplified DNA sequences in chromosomal regions other than chromosome 7p. From the prognostic point of view, these amplification profiles showed a significant impact on overall survival of glioblastoma multiforme patients (p>0.001). Based on these gene amplification profiles, a risk-stratification scoring system was built for prognostic stratification of glioblastoma which might be easily implemented in routine diagnostics, and potentially contribute to improved patient management. |
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Prognostic stratification of adult primary glioblastoma multiforme patients based on their tumor gene amplification profilesglioblastomaclassificationsubtypesgene amplificationsurvivalSeveral classification systems have been proposed to address genomic heterogeneity of glioblastoma multiforme, but they either showed limited prognostic value and/or are difficult to implement in routine diagnostics. Here we propose a prognostic stratification model for these primary tumors based on tumor gene amplification profiles, that might be easily implemented in routine diagnostics, and potentially improve the patients management. Gene amplification profiles were prospectively evaluated in 80 primary glioblastoma multiforme tumors using single-nucleotide polymorphism arrays and the results obtained validated in publicly available data from 267/347 cases. Gene amplification was detected in 45% of patients, and chromosome 7p11.2 including the EGFR gene, was the most frequently amplified chromosomal region - either alone (18%) or in combination with amplification of DNA sequences in other chromosomal regions (10% of cases). Other frequently amplified DNA sequences included regions in chromosomes 12q(10%), 4q12(7%) and 1q32.1(4%). Based on their gene amplification profiles, glioblastomas were subdivided into: i) tumors with no gene amplification (55%); ii) tumors with chromosome 7p/EGFR gene amplification (with or without amplification of other chromosomal regions) (38%); and iii) glioblastoma multiforme with a single (11%) or multiple (6%) amplified DNA sequences in chromosomal regions other than chromosome 7p. From the prognostic point of view, these amplification profiles showed a significant impact on overall survival of glioblastoma multiforme patients (p>0.001). Based on these gene amplification profiles, a risk-stratification scoring system was built for prognostic stratification of glioblastoma which might be easily implemented in routine diagnostics, and potentially contribute to improved patient management.This work was supported by RETICC RD06/0020/0035, RD06/0020/0059 and RD12/0036/0048 grants from Red Temática de Investigación Cooperativa en Cáncer (RTICC), Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, (Madrid, Spain and FONDOS FEDER), AES PI16/000476 (Instituto de Salud Carlos III, Madrid, Spain and FONDOS FEDER), GRS909A14 (JCYL) and CB16/12/00400 grant (CIBERONC, Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, Madrid, Spain and FONDOS FEDER).Impact Journals2018-06-15info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/107797http://hdl.handle.net/10316/107797https://doi.org/10.18632/oncotarget.25562eng1949-2553González-Tablas, MaríaCrespo, InêsVital, Ana LuísaOtero, ÁlvaroNieto, Ana BelénSousa, PabloPatino-Alonso, María CarmenCorchete, Luis AntonioTão, HermínioRebelo, OlindaBarbosa, MarcosAlmeida, Maria do RosárioGuedes, Ana FilipaLopes, Maria CelesteFrench, Pim J.Orfão, AlbertoTabernero, María Doloresinfo: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:RCAAP2023-08-17T14:18:54Zoai:estudogeral.uc.pt:10316/107797Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:24:06.383287Repositório 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 |
Prognostic stratification of adult primary glioblastoma multiforme patients based on their tumor gene amplification profiles |
title |
Prognostic stratification of adult primary glioblastoma multiforme patients based on their tumor gene amplification profiles |
spellingShingle |
Prognostic stratification of adult primary glioblastoma multiforme patients based on their tumor gene amplification profiles González-Tablas, María glioblastoma classification subtypes gene amplification survival |
title_short |
Prognostic stratification of adult primary glioblastoma multiforme patients based on their tumor gene amplification profiles |
title_full |
Prognostic stratification of adult primary glioblastoma multiforme patients based on their tumor gene amplification profiles |
title_fullStr |
Prognostic stratification of adult primary glioblastoma multiforme patients based on their tumor gene amplification profiles |
title_full_unstemmed |
Prognostic stratification of adult primary glioblastoma multiforme patients based on their tumor gene amplification profiles |
title_sort |
Prognostic stratification of adult primary glioblastoma multiforme patients based on their tumor gene amplification profiles |
author |
González-Tablas, María |
author_facet |
González-Tablas, María Crespo, Inês Vital, Ana Luísa Otero, Álvaro Nieto, Ana Belén Sousa, Pablo Patino-Alonso, María Carmen Corchete, Luis Antonio Tão, Hermínio Rebelo, Olinda Barbosa, Marcos Almeida, Maria do Rosário Guedes, Ana Filipa Lopes, Maria Celeste French, Pim J. Orfão, Alberto Tabernero, María Dolores |
author_role |
author |
author2 |
Crespo, Inês Vital, Ana Luísa Otero, Álvaro Nieto, Ana Belén Sousa, Pablo Patino-Alonso, María Carmen Corchete, Luis Antonio Tão, Hermínio Rebelo, Olinda Barbosa, Marcos Almeida, Maria do Rosário Guedes, Ana Filipa Lopes, Maria Celeste French, Pim J. Orfão, Alberto Tabernero, María Dolores |
author2_role |
author author author author author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
González-Tablas, María Crespo, Inês Vital, Ana Luísa Otero, Álvaro Nieto, Ana Belén Sousa, Pablo Patino-Alonso, María Carmen Corchete, Luis Antonio Tão, Hermínio Rebelo, Olinda Barbosa, Marcos Almeida, Maria do Rosário Guedes, Ana Filipa Lopes, Maria Celeste French, Pim J. Orfão, Alberto Tabernero, María Dolores |
dc.subject.por.fl_str_mv |
glioblastoma classification subtypes gene amplification survival |
topic |
glioblastoma classification subtypes gene amplification survival |
description |
Several classification systems have been proposed to address genomic heterogeneity of glioblastoma multiforme, but they either showed limited prognostic value and/or are difficult to implement in routine diagnostics. Here we propose a prognostic stratification model for these primary tumors based on tumor gene amplification profiles, that might be easily implemented in routine diagnostics, and potentially improve the patients management. Gene amplification profiles were prospectively evaluated in 80 primary glioblastoma multiforme tumors using single-nucleotide polymorphism arrays and the results obtained validated in publicly available data from 267/347 cases. Gene amplification was detected in 45% of patients, and chromosome 7p11.2 including the EGFR gene, was the most frequently amplified chromosomal region - either alone (18%) or in combination with amplification of DNA sequences in other chromosomal regions (10% of cases). Other frequently amplified DNA sequences included regions in chromosomes 12q(10%), 4q12(7%) and 1q32.1(4%). Based on their gene amplification profiles, glioblastomas were subdivided into: i) tumors with no gene amplification (55%); ii) tumors with chromosome 7p/EGFR gene amplification (with or without amplification of other chromosomal regions) (38%); and iii) glioblastoma multiforme with a single (11%) or multiple (6%) amplified DNA sequences in chromosomal regions other than chromosome 7p. From the prognostic point of view, these amplification profiles showed a significant impact on overall survival of glioblastoma multiforme patients (p>0.001). Based on these gene amplification profiles, a risk-stratification scoring system was built for prognostic stratification of glioblastoma which might be easily implemented in routine diagnostics, and potentially contribute to improved patient management. |
publishDate |
2018 |
dc.date.none.fl_str_mv |
2018-06-15 |
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/10316/107797 http://hdl.handle.net/10316/107797 https://doi.org/10.18632/oncotarget.25562 |
url |
http://hdl.handle.net/10316/107797 https://doi.org/10.18632/oncotarget.25562 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
1949-2553 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Impact Journals |
publisher.none.fl_str_mv |
Impact Journals |
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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RCAAP |
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RCAAP |
reponame_str |
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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