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Impact of CDKN2A/B Homozygous Deletion on the Prognosis and Biology of IDH-Mutant Glioma
Although hotspot mutations in isocitrate dehydrogenase (IDH) genes are associated with favorable clinical outcomes in glioma, CDKN2A/B homozygous deletion has been identified as an independent predicator of poor prognosis. Accordingly, the 2021 edition of the World Health Organization (WHO) classifi...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8869746/ https://www.ncbi.nlm.nih.gov/pubmed/35203456 http://dx.doi.org/10.3390/biomedicines10020246 |
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author | Huang, L. Eric |
author_facet | Huang, L. Eric |
author_sort | Huang, L. Eric |
collection | PubMed |
description | Although hotspot mutations in isocitrate dehydrogenase (IDH) genes are associated with favorable clinical outcomes in glioma, CDKN2A/B homozygous deletion has been identified as an independent predicator of poor prognosis. Accordingly, the 2021 edition of the World Health Organization (WHO) classification of tumors of the central nervous system (CNS) has adopted this molecular feature by upgrading IDH-mutant astrocytoma to CNS WHO grade IV, even in the absence of glioblastoma-specific histological features—necrosis and microvascular proliferation. This new entity of IDH-mutant astrocytoma not only signifies an exception to the generally favorable outcome of IDH-mutant glioma, but also brings into question whether, and, if so, how, CDKN2A/B homozygous deletion overrides the anti-tumor activity of IDH mutation by promoting the proliferation of stem/neural progenitor-like cells. Understanding the mechanism by which IDH mutation requires intact tumor-suppressor genes for conferring favorable outcome may improve therapeutics. |
format | Online Article Text |
id | pubmed-8869746 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-88697462022-02-25 Impact of CDKN2A/B Homozygous Deletion on the Prognosis and Biology of IDH-Mutant Glioma Huang, L. Eric Biomedicines Perspective Although hotspot mutations in isocitrate dehydrogenase (IDH) genes are associated with favorable clinical outcomes in glioma, CDKN2A/B homozygous deletion has been identified as an independent predicator of poor prognosis. Accordingly, the 2021 edition of the World Health Organization (WHO) classification of tumors of the central nervous system (CNS) has adopted this molecular feature by upgrading IDH-mutant astrocytoma to CNS WHO grade IV, even in the absence of glioblastoma-specific histological features—necrosis and microvascular proliferation. This new entity of IDH-mutant astrocytoma not only signifies an exception to the generally favorable outcome of IDH-mutant glioma, but also brings into question whether, and, if so, how, CDKN2A/B homozygous deletion overrides the anti-tumor activity of IDH mutation by promoting the proliferation of stem/neural progenitor-like cells. Understanding the mechanism by which IDH mutation requires intact tumor-suppressor genes for conferring favorable outcome may improve therapeutics. MDPI 2022-01-24 /pmc/articles/PMC8869746/ /pubmed/35203456 http://dx.doi.org/10.3390/biomedicines10020246 Text en © 2022 by the author. 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 | Perspective Huang, L. Eric Impact of CDKN2A/B Homozygous Deletion on the Prognosis and Biology of IDH-Mutant Glioma |
title | Impact of CDKN2A/B Homozygous Deletion on the Prognosis and Biology of IDH-Mutant Glioma |
title_full | Impact of CDKN2A/B Homozygous Deletion on the Prognosis and Biology of IDH-Mutant Glioma |
title_fullStr | Impact of CDKN2A/B Homozygous Deletion on the Prognosis and Biology of IDH-Mutant Glioma |
title_full_unstemmed | Impact of CDKN2A/B Homozygous Deletion on the Prognosis and Biology of IDH-Mutant Glioma |
title_short | Impact of CDKN2A/B Homozygous Deletion on the Prognosis and Biology of IDH-Mutant Glioma |
title_sort | impact of cdkn2a/b homozygous deletion on the prognosis and biology of idh-mutant glioma |
topic | Perspective |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8869746/ https://www.ncbi.nlm.nih.gov/pubmed/35203456 http://dx.doi.org/10.3390/biomedicines10020246 |
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