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Identification of Genetic Alterations in Rapid Progressive Glioblastoma by Use of Whole Exome Sequencing

Background: Glioblastoma poses an inevitable threat to patients despite aggressive therapy regimes. It displays a great level of molecular heterogeneity and numerous substitutions in several genes have been documented. Next-generation sequencing techniques have identified various molecular signature...

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Autores principales: Khan, Imran, Işık, Esra Büşra, Mahfooz, Sadaf, Khan, Asif M., Hatiboglu, Mustafa Aziz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10047503/
https://www.ncbi.nlm.nih.gov/pubmed/36980325
http://dx.doi.org/10.3390/diagnostics13061017
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author Khan, Imran
Işık, Esra Büşra
Mahfooz, Sadaf
Khan, Asif M.
Hatiboglu, Mustafa Aziz
author_facet Khan, Imran
Işık, Esra Büşra
Mahfooz, Sadaf
Khan, Asif M.
Hatiboglu, Mustafa Aziz
author_sort Khan, Imran
collection PubMed
description Background: Glioblastoma poses an inevitable threat to patients despite aggressive therapy regimes. It displays a great level of molecular heterogeneity and numerous substitutions in several genes have been documented. Next-generation sequencing techniques have identified various molecular signatures that have led to a better understanding of the molecular pathogenesis of glioblastoma. In this limited study, we sought to identify genetic variants in a small number of rare patients with aggressive glioblastoma. Methods: Five tumor tissue samples were isolated from four patients with rapidly growing glioblastoma. Genomic DNA was isolated and whole exome sequencing was used to study protein-coding regions. Generated FASTQ files were analyzed and variants were called for each sample. Variants were prioritized with different approaches and functional annotation was applied for the detrimental variants. Results: A total of 49,780 somatic variants were identified in the five glioblastoma samples studied, with the majority as missense substitutions. The top ten genes with the highest number of substitutions were MUC3A, MUC4, MUC6, OR4C5, PDE4DIP, AHNAK2, OR4C3, ZNF806, TTN, and RP1L1. Notably, variant prioritization after annotation indicated that the MTCH2 (Chr11: 47647265 A>G) gene sequence change was putative deleterious in all of the aggressive tumor samples. Conclusion: The MTCH2 (Chr11: 47647265 A>G) gene substitution was identified as putative deleterious in highly aggressive glioblastomas, which merits further investigation. Moreover, a high tumor mutation burden was observed, with a signature of the highest substitutions in MUC3A, MUC4, MUC6, OR4C5, PDE4DIP, AHNAK2, OR4C3, ZNF806, TTN, and RP1L1 genes. The findings provide critical, initial data for the further rational design of genetic screening and diagnostic approaches against aggressive glioblastoma.
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spelling pubmed-100475032023-03-29 Identification of Genetic Alterations in Rapid Progressive Glioblastoma by Use of Whole Exome Sequencing Khan, Imran Işık, Esra Büşra Mahfooz, Sadaf Khan, Asif M. Hatiboglu, Mustafa Aziz Diagnostics (Basel) Article Background: Glioblastoma poses an inevitable threat to patients despite aggressive therapy regimes. It displays a great level of molecular heterogeneity and numerous substitutions in several genes have been documented. Next-generation sequencing techniques have identified various molecular signatures that have led to a better understanding of the molecular pathogenesis of glioblastoma. In this limited study, we sought to identify genetic variants in a small number of rare patients with aggressive glioblastoma. Methods: Five tumor tissue samples were isolated from four patients with rapidly growing glioblastoma. Genomic DNA was isolated and whole exome sequencing was used to study protein-coding regions. Generated FASTQ files were analyzed and variants were called for each sample. Variants were prioritized with different approaches and functional annotation was applied for the detrimental variants. Results: A total of 49,780 somatic variants were identified in the five glioblastoma samples studied, with the majority as missense substitutions. The top ten genes with the highest number of substitutions were MUC3A, MUC4, MUC6, OR4C5, PDE4DIP, AHNAK2, OR4C3, ZNF806, TTN, and RP1L1. Notably, variant prioritization after annotation indicated that the MTCH2 (Chr11: 47647265 A>G) gene sequence change was putative deleterious in all of the aggressive tumor samples. Conclusion: The MTCH2 (Chr11: 47647265 A>G) gene substitution was identified as putative deleterious in highly aggressive glioblastomas, which merits further investigation. Moreover, a high tumor mutation burden was observed, with a signature of the highest substitutions in MUC3A, MUC4, MUC6, OR4C5, PDE4DIP, AHNAK2, OR4C3, ZNF806, TTN, and RP1L1 genes. The findings provide critical, initial data for the further rational design of genetic screening and diagnostic approaches against aggressive glioblastoma. MDPI 2023-03-07 /pmc/articles/PMC10047503/ /pubmed/36980325 http://dx.doi.org/10.3390/diagnostics13061017 Text en © 2023 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 Article
Khan, Imran
Işık, Esra Büşra
Mahfooz, Sadaf
Khan, Asif M.
Hatiboglu, Mustafa Aziz
Identification of Genetic Alterations in Rapid Progressive Glioblastoma by Use of Whole Exome Sequencing
title Identification of Genetic Alterations in Rapid Progressive Glioblastoma by Use of Whole Exome Sequencing
title_full Identification of Genetic Alterations in Rapid Progressive Glioblastoma by Use of Whole Exome Sequencing
title_fullStr Identification of Genetic Alterations in Rapid Progressive Glioblastoma by Use of Whole Exome Sequencing
title_full_unstemmed Identification of Genetic Alterations in Rapid Progressive Glioblastoma by Use of Whole Exome Sequencing
title_short Identification of Genetic Alterations in Rapid Progressive Glioblastoma by Use of Whole Exome Sequencing
title_sort identification of genetic alterations in rapid progressive glioblastoma by use of whole exome sequencing
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10047503/
https://www.ncbi.nlm.nih.gov/pubmed/36980325
http://dx.doi.org/10.3390/diagnostics13061017
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