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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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Autor principal: Huang, L. Eric
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
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
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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.
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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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