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Next-Generation Sequencing Comparative Analysis of DNA Mutations between Blood-Derived Extracellular Vesicles and Matched Cancer Tissue in Patients with Grade 4 Glioblastoma

The biological heterogeneity of glioblastoma, IDH-wildtype (GBM, CNS WHO grade 4), the most aggressive type of brain cancer, is a critical hallmark, caused by changes in the genomic mutational asset and influencing clinical progression over time. The understanding and monitoring of the mutational pr...

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Autores principales: Rosa, Paolo, De Falco, Elena, Pacini, Luca, Piazza, Amedeo, Ciracì, Paolo, Ricciardi, Luca, Fiorentino, Francesco, Trungu, Sokol, Miscusi, Massimo, Raco, Antonino, Calogero, Antonella
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9599233/
https://www.ncbi.nlm.nih.gov/pubmed/36289852
http://dx.doi.org/10.3390/biomedicines10102590
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author Rosa, Paolo
De Falco, Elena
Pacini, Luca
Piazza, Amedeo
Ciracì, Paolo
Ricciardi, Luca
Fiorentino, Francesco
Trungu, Sokol
Miscusi, Massimo
Raco, Antonino
Calogero, Antonella
author_facet Rosa, Paolo
De Falco, Elena
Pacini, Luca
Piazza, Amedeo
Ciracì, Paolo
Ricciardi, Luca
Fiorentino, Francesco
Trungu, Sokol
Miscusi, Massimo
Raco, Antonino
Calogero, Antonella
author_sort Rosa, Paolo
collection PubMed
description The biological heterogeneity of glioblastoma, IDH-wildtype (GBM, CNS WHO grade 4), the most aggressive type of brain cancer, is a critical hallmark, caused by changes in the genomic mutational asset and influencing clinical progression over time. The understanding and monitoring of the mutational profile is important not only to reveal novel therapeutic targets in this set of patients, but also to ameliorate the clinical stratification of subjects and the prognostic significance. As neurosurgery represents the primary technique to manage GBM, it is of utmost importance to optimize alternative and less invasive methods to monitor the dynamic mutation profile of these patients. Extracellular vesicles (EVs) are included in the liquid biopsy analysis and have emerged as the biological mirror of escaping and surviving mechanisms by many tumors, including glioblastoma. Very few studies have investigated the technical feasibility to detect and analyze the genomic profile by Next-Generation Sequencing (UMI system) in circulating EVs of patients with grade IV glioblastoma. Here, we attempted to characterize and to compare the corresponding matched tissue samples and potential variants with pathogenic significance of the DNA contained in peripheral-blood-derived EVs. The NGS analysis has revealed that patients with grade IV glioblastoma exhibited lesser DNA content in EVs than controls and that, both in EVs and matched cancer tissues, the NF1 gene was consistently mutated in all patients, with the c.2568C>G as the most common pathogenic variant expressed. This study supports the clinical utility of circulating EVs in glioblastoma as an eligible tool for personalized medicine.
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spelling pubmed-95992332022-10-27 Next-Generation Sequencing Comparative Analysis of DNA Mutations between Blood-Derived Extracellular Vesicles and Matched Cancer Tissue in Patients with Grade 4 Glioblastoma Rosa, Paolo De Falco, Elena Pacini, Luca Piazza, Amedeo Ciracì, Paolo Ricciardi, Luca Fiorentino, Francesco Trungu, Sokol Miscusi, Massimo Raco, Antonino Calogero, Antonella Biomedicines Brief Report The biological heterogeneity of glioblastoma, IDH-wildtype (GBM, CNS WHO grade 4), the most aggressive type of brain cancer, is a critical hallmark, caused by changes in the genomic mutational asset and influencing clinical progression over time. The understanding and monitoring of the mutational profile is important not only to reveal novel therapeutic targets in this set of patients, but also to ameliorate the clinical stratification of subjects and the prognostic significance. As neurosurgery represents the primary technique to manage GBM, it is of utmost importance to optimize alternative and less invasive methods to monitor the dynamic mutation profile of these patients. Extracellular vesicles (EVs) are included in the liquid biopsy analysis and have emerged as the biological mirror of escaping and surviving mechanisms by many tumors, including glioblastoma. Very few studies have investigated the technical feasibility to detect and analyze the genomic profile by Next-Generation Sequencing (UMI system) in circulating EVs of patients with grade IV glioblastoma. Here, we attempted to characterize and to compare the corresponding matched tissue samples and potential variants with pathogenic significance of the DNA contained in peripheral-blood-derived EVs. The NGS analysis has revealed that patients with grade IV glioblastoma exhibited lesser DNA content in EVs than controls and that, both in EVs and matched cancer tissues, the NF1 gene was consistently mutated in all patients, with the c.2568C>G as the most common pathogenic variant expressed. This study supports the clinical utility of circulating EVs in glioblastoma as an eligible tool for personalized medicine. MDPI 2022-10-15 /pmc/articles/PMC9599233/ /pubmed/36289852 http://dx.doi.org/10.3390/biomedicines10102590 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Brief Report
Rosa, Paolo
De Falco, Elena
Pacini, Luca
Piazza, Amedeo
Ciracì, Paolo
Ricciardi, Luca
Fiorentino, Francesco
Trungu, Sokol
Miscusi, Massimo
Raco, Antonino
Calogero, Antonella
Next-Generation Sequencing Comparative Analysis of DNA Mutations between Blood-Derived Extracellular Vesicles and Matched Cancer Tissue in Patients with Grade 4 Glioblastoma
title Next-Generation Sequencing Comparative Analysis of DNA Mutations between Blood-Derived Extracellular Vesicles and Matched Cancer Tissue in Patients with Grade 4 Glioblastoma
title_full Next-Generation Sequencing Comparative Analysis of DNA Mutations between Blood-Derived Extracellular Vesicles and Matched Cancer Tissue in Patients with Grade 4 Glioblastoma
title_fullStr Next-Generation Sequencing Comparative Analysis of DNA Mutations between Blood-Derived Extracellular Vesicles and Matched Cancer Tissue in Patients with Grade 4 Glioblastoma
title_full_unstemmed Next-Generation Sequencing Comparative Analysis of DNA Mutations between Blood-Derived Extracellular Vesicles and Matched Cancer Tissue in Patients with Grade 4 Glioblastoma
title_short Next-Generation Sequencing Comparative Analysis of DNA Mutations between Blood-Derived Extracellular Vesicles and Matched Cancer Tissue in Patients with Grade 4 Glioblastoma
title_sort next-generation sequencing comparative analysis of dna mutations between blood-derived extracellular vesicles and matched cancer tissue in patients with grade 4 glioblastoma
topic Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9599233/
https://www.ncbi.nlm.nih.gov/pubmed/36289852
http://dx.doi.org/10.3390/biomedicines10102590
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