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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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) |
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glioblastoma astrocytoma oligodendroglioma H3.1/H3.2 H3.3 <i>H3F3B</i> Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 |
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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 |
work_keys_str_mv |
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