Cargando…
Prognostic stratification of adult primary glioblastoma multiforme patients based on their tumor gene amplification profiles
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...
Autores principales: | , , , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6021328/ https://www.ncbi.nlm.nih.gov/pubmed/29963263 http://dx.doi.org/10.18632/oncotarget.25562 |
_version_ | 1783335446054436864 |
---|---|
author | 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 Rosário Guedes, Ana Filipa Lopes, María Celeste French, Pim J. Orfao, Alberto Tabernero, María Dolores |
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 Rosário Guedes, Ana Filipa Lopes, María Celeste French, Pim J. Orfao, Alberto Tabernero, María Dolores |
author_sort | González-Tablas, María |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-6021328 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-60213282018-06-30 Prognostic stratification of adult primary glioblastoma multiforme patients based on their tumor gene amplification profiles 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 Rosário Guedes, Ana Filipa Lopes, María Celeste French, Pim J. Orfao, Alberto Tabernero, María Dolores Oncotarget Research Paper 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. Impact Journals LLC 2018-06-15 /pmc/articles/PMC6021328/ /pubmed/29963263 http://dx.doi.org/10.18632/oncotarget.25562 Text en Copyright: © 2018 González-Tablas et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (http://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper 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 Rosário Guedes, Ana Filipa Lopes, María Celeste French, Pim J. Orfao, Alberto Tabernero, María Dolores 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 |
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_short | 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 |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6021328/ https://www.ncbi.nlm.nih.gov/pubmed/29963263 http://dx.doi.org/10.18632/oncotarget.25562 |
work_keys_str_mv | AT gonzaleztablasmaria prognosticstratificationofadultprimaryglioblastomamultiformepatientsbasedontheirtumorgeneamplificationprofiles AT crespoines prognosticstratificationofadultprimaryglioblastomamultiformepatientsbasedontheirtumorgeneamplificationprofiles AT vitalanaluisa prognosticstratificationofadultprimaryglioblastomamultiformepatientsbasedontheirtumorgeneamplificationprofiles AT oteroalvaro prognosticstratificationofadultprimaryglioblastomamultiformepatientsbasedontheirtumorgeneamplificationprofiles AT nietoanabelen prognosticstratificationofadultprimaryglioblastomamultiformepatientsbasedontheirtumorgeneamplificationprofiles AT sousapablo prognosticstratificationofadultprimaryglioblastomamultiformepatientsbasedontheirtumorgeneamplificationprofiles AT patinoalonsomariacarmen prognosticstratificationofadultprimaryglioblastomamultiformepatientsbasedontheirtumorgeneamplificationprofiles AT corcheteluisantonio prognosticstratificationofadultprimaryglioblastomamultiformepatientsbasedontheirtumorgeneamplificationprofiles AT taoherminio prognosticstratificationofadultprimaryglioblastomamultiformepatientsbasedontheirtumorgeneamplificationprofiles AT rebeloolinda prognosticstratificationofadultprimaryglioblastomamultiformepatientsbasedontheirtumorgeneamplificationprofiles AT barbosamarcos prognosticstratificationofadultprimaryglioblastomamultiformepatientsbasedontheirtumorgeneamplificationprofiles AT almeidamariarosario prognosticstratificationofadultprimaryglioblastomamultiformepatientsbasedontheirtumorgeneamplificationprofiles AT guedesanafilipa prognosticstratificationofadultprimaryglioblastomamultiformepatientsbasedontheirtumorgeneamplificationprofiles AT lopesmariaceleste prognosticstratificationofadultprimaryglioblastomamultiformepatientsbasedontheirtumorgeneamplificationprofiles AT frenchpimj prognosticstratificationofadultprimaryglioblastomamultiformepatientsbasedontheirtumorgeneamplificationprofiles AT orfaoalberto prognosticstratificationofadultprimaryglioblastomamultiformepatientsbasedontheirtumorgeneamplificationprofiles AT taberneromariadolores prognosticstratificationofadultprimaryglioblastomamultiformepatientsbasedontheirtumorgeneamplificationprofiles |