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Heterogeneous EGFR, CDK4, MDM4, and PDGFRA Gene Expression Profiles in Primary GBM: No Association with Patient Survival
Background: The prognostic impact of the expression profile of genes recurrently amplified in glioblastoma multiforme (GBM) remains controversial. Methods: We investigated the RNA gene expression profile of epidermal growth factor receptor (EGFR), cyclin-dependent kinase 4 (CDK4), murine doble minut...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016708/ https://www.ncbi.nlm.nih.gov/pubmed/31963499 http://dx.doi.org/10.3390/cancers12010231 |
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author | González-Tablas, María Arandia, Daniel Jara-Acevedo, María Otero, Álvaro Vital, Ana-Luisa Prieto, Carlos González-Garcia, Nerea Nieto-Librero, Ana Belén Tao, Herminio Pascual, Daniel Ruiz, Laura Sousa, Pablo Galindo-Villardón, Purificación Orfao, Alberto Tabernero, María Dolores |
author_facet | González-Tablas, María Arandia, Daniel Jara-Acevedo, María Otero, Álvaro Vital, Ana-Luisa Prieto, Carlos González-Garcia, Nerea Nieto-Librero, Ana Belén Tao, Herminio Pascual, Daniel Ruiz, Laura Sousa, Pablo Galindo-Villardón, Purificación Orfao, Alberto Tabernero, María Dolores |
author_sort | González-Tablas, María |
collection | PubMed |
description | Background: The prognostic impact of the expression profile of genes recurrently amplified in glioblastoma multiforme (GBM) remains controversial. Methods: We investigated the RNA gene expression profile of epidermal growth factor receptor (EGFR), cyclin-dependent kinase 4 (CDK4), murine doble minute 4 (MDM4), and platelet derived growth factor receptor alpha (PDGFRA) in 83 primary GBM tumors vs. 42 normal brain tissue samples. Interphase FISH (iFISH) analysis for the four genes, together with analysis of intragenic deletions in EGFR and PDGFRA, were evaluated in parallel at the DNA level. As validation cohort, publicly available RNA gene expression data on 293 samples from 10 different GBM patient series were also studied. Results: At the RNA level, CDK4 was the most frequently overexpressed gene (90%) followed by EGFR (58%) and PDGFRA (58%). Chromosome 7 copy number alterations, i.e., trisomy (49%) and polysomy (44%), showed no clear association with EGFR gene expression levels. In turn, intragenic EGFR deletions were found in 39 patients (47%), including EGFRvIII (46%) in association with EGFRvIVa (4%), EGFRvII (2%) or other EGFR deletions (3%) and PDGFRA deletion of exons 8–9 was found in only two tumors (2%). Conclusions: Overall, none of the gene expression profiles and/or intragenic EGFR deletions showed a significant impact on overall survival of GBM supporting the notion that other still unraveled features of the disease might play a more relevant prognostic role in GBM. |
format | Online Article Text |
id | pubmed-7016708 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-70167082020-02-28 Heterogeneous EGFR, CDK4, MDM4, and PDGFRA Gene Expression Profiles in Primary GBM: No Association with Patient Survival González-Tablas, María Arandia, Daniel Jara-Acevedo, María Otero, Álvaro Vital, Ana-Luisa Prieto, Carlos González-Garcia, Nerea Nieto-Librero, Ana Belén Tao, Herminio Pascual, Daniel Ruiz, Laura Sousa, Pablo Galindo-Villardón, Purificación Orfao, Alberto Tabernero, María Dolores Cancers (Basel) Article Background: The prognostic impact of the expression profile of genes recurrently amplified in glioblastoma multiforme (GBM) remains controversial. Methods: We investigated the RNA gene expression profile of epidermal growth factor receptor (EGFR), cyclin-dependent kinase 4 (CDK4), murine doble minute 4 (MDM4), and platelet derived growth factor receptor alpha (PDGFRA) in 83 primary GBM tumors vs. 42 normal brain tissue samples. Interphase FISH (iFISH) analysis for the four genes, together with analysis of intragenic deletions in EGFR and PDGFRA, were evaluated in parallel at the DNA level. As validation cohort, publicly available RNA gene expression data on 293 samples from 10 different GBM patient series were also studied. Results: At the RNA level, CDK4 was the most frequently overexpressed gene (90%) followed by EGFR (58%) and PDGFRA (58%). Chromosome 7 copy number alterations, i.e., trisomy (49%) and polysomy (44%), showed no clear association with EGFR gene expression levels. In turn, intragenic EGFR deletions were found in 39 patients (47%), including EGFRvIII (46%) in association with EGFRvIVa (4%), EGFRvII (2%) or other EGFR deletions (3%) and PDGFRA deletion of exons 8–9 was found in only two tumors (2%). Conclusions: Overall, none of the gene expression profiles and/or intragenic EGFR deletions showed a significant impact on overall survival of GBM supporting the notion that other still unraveled features of the disease might play a more relevant prognostic role in GBM. MDPI 2020-01-17 /pmc/articles/PMC7016708/ /pubmed/31963499 http://dx.doi.org/10.3390/cancers12010231 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article González-Tablas, María Arandia, Daniel Jara-Acevedo, María Otero, Álvaro Vital, Ana-Luisa Prieto, Carlos González-Garcia, Nerea Nieto-Librero, Ana Belén Tao, Herminio Pascual, Daniel Ruiz, Laura Sousa, Pablo Galindo-Villardón, Purificación Orfao, Alberto Tabernero, María Dolores Heterogeneous EGFR, CDK4, MDM4, and PDGFRA Gene Expression Profiles in Primary GBM: No Association with Patient Survival |
title | Heterogeneous EGFR, CDK4, MDM4, and PDGFRA Gene Expression Profiles in Primary GBM: No Association with Patient Survival |
title_full | Heterogeneous EGFR, CDK4, MDM4, and PDGFRA Gene Expression Profiles in Primary GBM: No Association with Patient Survival |
title_fullStr | Heterogeneous EGFR, CDK4, MDM4, and PDGFRA Gene Expression Profiles in Primary GBM: No Association with Patient Survival |
title_full_unstemmed | Heterogeneous EGFR, CDK4, MDM4, and PDGFRA Gene Expression Profiles in Primary GBM: No Association with Patient Survival |
title_short | Heterogeneous EGFR, CDK4, MDM4, and PDGFRA Gene Expression Profiles in Primary GBM: No Association with Patient Survival |
title_sort | heterogeneous egfr, cdk4, mdm4, and pdgfra gene expression profiles in primary gbm: no association with patient survival |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7016708/ https://www.ncbi.nlm.nih.gov/pubmed/31963499 http://dx.doi.org/10.3390/cancers12010231 |
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