Potential Diagnostic Value of the Differential Expression of Histone H3 Variants between Low- and High-Grade Gliomas

Glioblastoma (GB) is the most aggressive form of glioma and is characterized by poor prognosis and high recurrence despite intensive clinical interventions. To retrieve the key factors underlying the high malignancy of GB with potential diagnosis utility, we combined the analysis of The Cancer Gene...

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Autores principales: Irati Hervás-Corpión, Andrea Gallardo-Orihuela, Inmaculada Catalina-Fernández, Irene Iglesias-Lozano, Olga Soto-Torres, Noelia Geribaldi-Doldán, Samuel Domínguez-García, Nuria Luna-García, Raquel Romero-García, Francisco Mora-López, Marianela Iriarte-Gahete, Jorge C. Morales, Antonio Campos-Caro, Carmen Castro, José L. Gil-Salú, Luis M. Valor
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Publicado: MDPI AG 2021
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spelling oai:doaj.org-article:73b0fb4161a44e2784a72fd6c4b0d1f92021-11-11T15:26:38ZPotential Diagnostic Value of the Differential Expression of Histone H3 Variants between Low- and High-Grade Gliomas10.3390/cancers132152612072-6694https://doaj.org/article/73b0fb4161a44e2784a72fd6c4b0d1f92021-10-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5261https://doaj.org/toc/2072-6694Glioblastoma (GB) is the most aggressive form of glioma and is characterized by poor prognosis and high recurrence despite intensive clinical interventions. To retrieve the key factors underlying the high malignancy of GB with potential diagnosis utility, we combined the analysis of The Cancer Gene Atlas and the REMBRANDT datasets plus a molecular examination of our own collection of surgical tumor resections. We determined a net reduction in the levels of the non-canonical histone H3 variant H3.3 in GB compared to lower-grade astrocytomas and oligodendrogliomas with a concomitant increase in the levels of the canonical histone H3 variants H3.1/H3.2. This increase can be potentially useful in the clinical diagnosis of high-grade gliomas, as evidenced by an immunohistochemistry screening of our cohort and can be at least partially explained by the induction of multiple histone genes encoding these canonical forms. Moreover, GBs showing low bulk levels of the H3.1/H3.2 proteins were more transcriptionally similar to low-grade gliomas than GBs showing high levels of H3.1/H3.2. In conclusion, this study identifies an imbalanced ratio between the H3 variants associated with glioma malignancy and molecular patterns relevant to the biology of gliomas, and proposes the examination of the H3.3 and H3.1/H3.2 levels to further refine diagnosis of low- and high-grade gliomas in future studies.Irati Hervás-CorpiónAndrea Gallardo-OrihuelaInmaculada Catalina-FernándezIrene Iglesias-LozanoOlga Soto-TorresNoelia Geribaldi-DoldánSamuel Domínguez-GarcíaNuria Luna-GarcíaRaquel Romero-GarcíaFrancisco Mora-LópezMarianela Iriarte-GaheteJorge C. MoralesAntonio Campos-CaroCarmen CastroJosé L. Gil-SalúLuis M. ValorMDPI AGarticleglioblastomaastrocytomaoligodendrogliomaH3.1/H3.2H3.3<i>H3F3B</i>Neoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5261, p 5261 (2021)
institution DOAJ
collection DOAJ
language EN
topic glioblastoma
astrocytoma
oligodendroglioma
H3.1/H3.2
H3.3
<i>H3F3B</i>
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
spellingShingle glioblastoma
astrocytoma
oligodendroglioma
H3.1/H3.2
H3.3
<i>H3F3B</i>
Neoplasms. Tumors. Oncology. Including cancer and carcinogens
RC254-282
Irati Hervás-Corpión
Andrea Gallardo-Orihuela
Inmaculada Catalina-Fernández
Irene Iglesias-Lozano
Olga Soto-Torres
Noelia Geribaldi-Doldán
Samuel Domínguez-García
Nuria Luna-García
Raquel Romero-García
Francisco Mora-López
Marianela Iriarte-Gahete
Jorge C. Morales
Antonio Campos-Caro
Carmen Castro
José L. Gil-Salú
Luis M. Valor
Potential Diagnostic Value of the Differential Expression of Histone H3 Variants between Low- and High-Grade Gliomas
description Glioblastoma (GB) is the most aggressive form of glioma and is characterized by poor prognosis and high recurrence despite intensive clinical interventions. To retrieve the key factors underlying the high malignancy of GB with potential diagnosis utility, we combined the analysis of The Cancer Gene Atlas and the REMBRANDT datasets plus a molecular examination of our own collection of surgical tumor resections. We determined a net reduction in the levels of the non-canonical histone H3 variant H3.3 in GB compared to lower-grade astrocytomas and oligodendrogliomas with a concomitant increase in the levels of the canonical histone H3 variants H3.1/H3.2. This increase can be potentially useful in the clinical diagnosis of high-grade gliomas, as evidenced by an immunohistochemistry screening of our cohort and can be at least partially explained by the induction of multiple histone genes encoding these canonical forms. Moreover, GBs showing low bulk levels of the H3.1/H3.2 proteins were more transcriptionally similar to low-grade gliomas than GBs showing high levels of H3.1/H3.2. In conclusion, this study identifies an imbalanced ratio between the H3 variants associated with glioma malignancy and molecular patterns relevant to the biology of gliomas, and proposes the examination of the H3.3 and H3.1/H3.2 levels to further refine diagnosis of low- and high-grade gliomas in future studies.
format article
author Irati Hervás-Corpión
Andrea Gallardo-Orihuela
Inmaculada Catalina-Fernández
Irene Iglesias-Lozano
Olga Soto-Torres
Noelia Geribaldi-Doldán
Samuel Domínguez-García
Nuria Luna-García
Raquel Romero-García
Francisco Mora-López
Marianela Iriarte-Gahete
Jorge C. Morales
Antonio Campos-Caro
Carmen Castro
José L. Gil-Salú
Luis M. Valor
author_facet Irati Hervás-Corpión
Andrea Gallardo-Orihuela
Inmaculada Catalina-Fernández
Irene Iglesias-Lozano
Olga Soto-Torres
Noelia Geribaldi-Doldán
Samuel Domínguez-García
Nuria Luna-García
Raquel Romero-García
Francisco Mora-López
Marianela Iriarte-Gahete
Jorge C. Morales
Antonio Campos-Caro
Carmen Castro
José L. Gil-Salú
Luis M. Valor
author_sort Irati Hervás-Corpión
title Potential Diagnostic Value of the Differential Expression of Histone H3 Variants between Low- and High-Grade Gliomas
title_short Potential Diagnostic Value of the Differential Expression of Histone H3 Variants between Low- and High-Grade Gliomas
title_full Potential Diagnostic Value of the Differential Expression of Histone H3 Variants between Low- and High-Grade Gliomas
title_fullStr Potential Diagnostic Value of the Differential Expression of Histone H3 Variants between Low- and High-Grade Gliomas
title_full_unstemmed Potential Diagnostic Value of the Differential Expression of Histone H3 Variants between Low- and High-Grade Gliomas
title_sort potential diagnostic value of the differential expression of histone h3 variants between low- and high-grade gliomas
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/73b0fb4161a44e2784a72fd6c4b0d1f9
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