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Polysome Profiling of a Human Glioblastoma Reveals Intratumoral Heterogeneity
Glioblastoma (GBM) is one of the most aggressive cancers, with median survival of less than 2 years. Despite of considerable advance in molecular classification of GBMs, no improvements in therapy have been described. The scenario is further complicated by tumor heterogeneity and the relationship am...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6539516/ https://www.ncbi.nlm.nih.gov/pubmed/31052505 http://dx.doi.org/10.3390/ijms20092177 |
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author | Lupinacci, Fernanda Cristina Sulla Kuasne, Hellen Roffé, Martin Vassalakis, Julia Avian da Silva, Fernanda Ferreira Santos, Tiago Góss Andrade, Victor Piana Sanematsu, Paulo Martins, Vilma Regina Rogatto, Silvia Regina Hajj, Glaucia Noeli Maroso |
author_facet | Lupinacci, Fernanda Cristina Sulla Kuasne, Hellen Roffé, Martin Vassalakis, Julia Avian da Silva, Fernanda Ferreira Santos, Tiago Góss Andrade, Victor Piana Sanematsu, Paulo Martins, Vilma Regina Rogatto, Silvia Regina Hajj, Glaucia Noeli Maroso |
author_sort | Lupinacci, Fernanda Cristina Sulla |
collection | PubMed |
description | Glioblastoma (GBM) is one of the most aggressive cancers, with median survival of less than 2 years. Despite of considerable advance in molecular classification of GBMs, no improvements in therapy have been described. The scenario is further complicated by tumor heterogeneity and the relationship among genetic, transcriptional and functional findings. Classically, gene expression has been evaluated by steady-state mRNA, however, this does not take translational control into consideration, which contributes considerably to the composition of the proteome. In this study, we evaluated the transcriptomic and translatomic signature of a GBM obtained from a single patient focusing in tumor heterogeneity. In a sampling of eight fragments, we investigated the translation rates, mTORC1 and ERK1/2 pathways and identified both total and polysome associated mRNAs. An increased translation rate was observed in fragments with high-grade histological features. High-grade histology was also associated with the expression of genes related to extracellular matrix (ECM) and angiogenesis, in both transcriptomes and translatomes. However, genes associated with epithelial to mesenchymal transition and stress response, were observed only in translatomes from high-grade fragments. Overall, our results demonstrate that isolation of translated mRNA can be used to identify biomarkers and reveal previously unrecognized determinants of heterogeneity in GBMs. |
format | Online Article Text |
id | pubmed-6539516 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-65395162019-06-04 Polysome Profiling of a Human Glioblastoma Reveals Intratumoral Heterogeneity Lupinacci, Fernanda Cristina Sulla Kuasne, Hellen Roffé, Martin Vassalakis, Julia Avian da Silva, Fernanda Ferreira Santos, Tiago Góss Andrade, Victor Piana Sanematsu, Paulo Martins, Vilma Regina Rogatto, Silvia Regina Hajj, Glaucia Noeli Maroso Int J Mol Sci Article Glioblastoma (GBM) is one of the most aggressive cancers, with median survival of less than 2 years. Despite of considerable advance in molecular classification of GBMs, no improvements in therapy have been described. The scenario is further complicated by tumor heterogeneity and the relationship among genetic, transcriptional and functional findings. Classically, gene expression has been evaluated by steady-state mRNA, however, this does not take translational control into consideration, which contributes considerably to the composition of the proteome. In this study, we evaluated the transcriptomic and translatomic signature of a GBM obtained from a single patient focusing in tumor heterogeneity. In a sampling of eight fragments, we investigated the translation rates, mTORC1 and ERK1/2 pathways and identified both total and polysome associated mRNAs. An increased translation rate was observed in fragments with high-grade histological features. High-grade histology was also associated with the expression of genes related to extracellular matrix (ECM) and angiogenesis, in both transcriptomes and translatomes. However, genes associated with epithelial to mesenchymal transition and stress response, were observed only in translatomes from high-grade fragments. Overall, our results demonstrate that isolation of translated mRNA can be used to identify biomarkers and reveal previously unrecognized determinants of heterogeneity in GBMs. MDPI 2019-05-02 /pmc/articles/PMC6539516/ /pubmed/31052505 http://dx.doi.org/10.3390/ijms20092177 Text en © 2019 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 Lupinacci, Fernanda Cristina Sulla Kuasne, Hellen Roffé, Martin Vassalakis, Julia Avian da Silva, Fernanda Ferreira Santos, Tiago Góss Andrade, Victor Piana Sanematsu, Paulo Martins, Vilma Regina Rogatto, Silvia Regina Hajj, Glaucia Noeli Maroso Polysome Profiling of a Human Glioblastoma Reveals Intratumoral Heterogeneity |
title | Polysome Profiling of a Human Glioblastoma Reveals Intratumoral Heterogeneity |
title_full | Polysome Profiling of a Human Glioblastoma Reveals Intratumoral Heterogeneity |
title_fullStr | Polysome Profiling of a Human Glioblastoma Reveals Intratumoral Heterogeneity |
title_full_unstemmed | Polysome Profiling of a Human Glioblastoma Reveals Intratumoral Heterogeneity |
title_short | Polysome Profiling of a Human Glioblastoma Reveals Intratumoral Heterogeneity |
title_sort | polysome profiling of a human glioblastoma reveals intratumoral heterogeneity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6539516/ https://www.ncbi.nlm.nih.gov/pubmed/31052505 http://dx.doi.org/10.3390/ijms20092177 |
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