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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
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.
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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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