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Somatic copy number alterations are associated with EGFR amplification and shortened survival in patients with primary glioblastoma
Glioblastoma (GBM) is the most common malignant primary tumor of the central nervous system. With no effective therapy, the prognosis for patients is terrible poor. It is highly heterogeneous and EGFR amplification is its most frequent molecular alteration. In this light, we aimed to examine the gen...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Neoplasia Press
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6864306/ https://www.ncbi.nlm.nih.gov/pubmed/31751860 http://dx.doi.org/10.1016/j.neo.2019.09.001 |
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author | Muñoz-Hidalgo, Lisandra San-Miguel, Teresa Megías, Javier Monleón, Daniel Navarro, Lara Roldán, Pedro Cerdá-Nicolás, Miguel López-Ginés, Concha |
author_facet | Muñoz-Hidalgo, Lisandra San-Miguel, Teresa Megías, Javier Monleón, Daniel Navarro, Lara Roldán, Pedro Cerdá-Nicolás, Miguel López-Ginés, Concha |
author_sort | Muñoz-Hidalgo, Lisandra |
collection | PubMed |
description | Glioblastoma (GBM) is the most common malignant primary tumor of the central nervous system. With no effective therapy, the prognosis for patients is terrible poor. It is highly heterogeneous and EGFR amplification is its most frequent molecular alteration. In this light, we aimed to examine the genetic heterogeneity of GBM and to correlate it with the clinical characteristics of the patients. For that purpose, we analyzed the status of EGFR and the somatic copy number alterations (CNAs) of a set of tumor suppressor genes and oncogenes. Thus, we found GBMs with high level of EGFR amplification, low level and with no EGFR amplification. Highly amplified tumors showed histological features of aggressiveness. Interestingly, accumulation of CNAs, as a measure of tumor mutational burden, was frequent and significantly associated to shortened survival. EGFR-amplified GBMs displayed both a higher number of concrete CNAs and a higher global tumor mutational burden than their no EGFR-amplified counterparts. In addition to genetic changes previously described in GBM, we found PARK2 and LARGE1 CNAs associated to EGFR amplification. The set of genes analyzed allowed us to explore relevant signaling pathways on GBM. Both PARK2 and LARGE1 are related to receptor tyrosine kinase/PI3K/PTEN/AKT/mTOR-signaling pathway. Finally, we found an association between the molecular pathways altered, EGFR amplification and a poor outcome. Our results underline the potential interest of categorizing GBM according to their EGFR amplification level and the usefulness of assessing the tumor mutational burden. These approaches would open new knowledge possibilities related to GBM biology and therapy. |
format | Online Article Text |
id | pubmed-6864306 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Neoplasia Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-68643062019-11-22 Somatic copy number alterations are associated with EGFR amplification and shortened survival in patients with primary glioblastoma Muñoz-Hidalgo, Lisandra San-Miguel, Teresa Megías, Javier Monleón, Daniel Navarro, Lara Roldán, Pedro Cerdá-Nicolás, Miguel López-Ginés, Concha Neoplasia Original article Glioblastoma (GBM) is the most common malignant primary tumor of the central nervous system. With no effective therapy, the prognosis for patients is terrible poor. It is highly heterogeneous and EGFR amplification is its most frequent molecular alteration. In this light, we aimed to examine the genetic heterogeneity of GBM and to correlate it with the clinical characteristics of the patients. For that purpose, we analyzed the status of EGFR and the somatic copy number alterations (CNAs) of a set of tumor suppressor genes and oncogenes. Thus, we found GBMs with high level of EGFR amplification, low level and with no EGFR amplification. Highly amplified tumors showed histological features of aggressiveness. Interestingly, accumulation of CNAs, as a measure of tumor mutational burden, was frequent and significantly associated to shortened survival. EGFR-amplified GBMs displayed both a higher number of concrete CNAs and a higher global tumor mutational burden than their no EGFR-amplified counterparts. In addition to genetic changes previously described in GBM, we found PARK2 and LARGE1 CNAs associated to EGFR amplification. The set of genes analyzed allowed us to explore relevant signaling pathways on GBM. Both PARK2 and LARGE1 are related to receptor tyrosine kinase/PI3K/PTEN/AKT/mTOR-signaling pathway. Finally, we found an association between the molecular pathways altered, EGFR amplification and a poor outcome. Our results underline the potential interest of categorizing GBM according to their EGFR amplification level and the usefulness of assessing the tumor mutational burden. These approaches would open new knowledge possibilities related to GBM biology and therapy. Neoplasia Press 2019-11-18 /pmc/articles/PMC6864306/ /pubmed/31751860 http://dx.doi.org/10.1016/j.neo.2019.09.001 Text en © 2019 Neoplasia Press, Inc. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original article Muñoz-Hidalgo, Lisandra San-Miguel, Teresa Megías, Javier Monleón, Daniel Navarro, Lara Roldán, Pedro Cerdá-Nicolás, Miguel López-Ginés, Concha Somatic copy number alterations are associated with EGFR amplification and shortened survival in patients with primary glioblastoma |
title | Somatic copy number alterations are associated with EGFR amplification and shortened survival in patients with primary glioblastoma |
title_full | Somatic copy number alterations are associated with EGFR amplification and shortened survival in patients with primary glioblastoma |
title_fullStr | Somatic copy number alterations are associated with EGFR amplification and shortened survival in patients with primary glioblastoma |
title_full_unstemmed | Somatic copy number alterations are associated with EGFR amplification and shortened survival in patients with primary glioblastoma |
title_short | Somatic copy number alterations are associated with EGFR amplification and shortened survival in patients with primary glioblastoma |
title_sort | somatic copy number alterations are associated with egfr amplification and shortened survival in patients with primary glioblastoma |
topic | Original article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6864306/ https://www.ncbi.nlm.nih.gov/pubmed/31751860 http://dx.doi.org/10.1016/j.neo.2019.09.001 |
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