Histone H3K27M Mutation Overrides Histological Grading in Pediatric Gliomas

Abstract Pediatric high-grade gliomas (HGG) are rare aggressive tumors that present a prognostic and therapeutic challenge. Diffuse midline glioma, H3K27M–mutant is a new entity introduced to HGG in the latest WHO classification. In this study we evaluated the presence of H3K27M mutation in 105 tumo...

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Autores principales:	Amal Mosaab, Moatasem El-Ayadi, Eman N. Khorshed, Nada Amer, Amal Refaat, Mohamed El-Beltagy, Zeinab Hassan, Sameh H. Soror, Mohamed Saad Zaghloul, Shahenda El-Naggar
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/8a04d8c9e4a441e288eb794de5590171
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spelling	oai:doaj.org-article:8a04d8c9e4a441e288eb794de55901712021-12-02T14:58:53ZHistone H3K27M Mutation Overrides Histological Grading in Pediatric Gliomas10.1038/s41598-020-65272-x2045-2322https://doaj.org/article/8a04d8c9e4a441e288eb794de55901712020-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-65272-xhttps://doaj.org/toc/2045-2322Abstract Pediatric high-grade gliomas (HGG) are rare aggressive tumors that present a prognostic and therapeutic challenge. Diffuse midline glioma, H3K27M–mutant is a new entity introduced to HGG in the latest WHO classification. In this study we evaluated the presence of H3K27M mutation in 105 tumor samples histologically classified into low-grade gliomas (LGG) (n = 45), and HGG (n = 60). Samples were screened for the mutation in histone H3.3 and H3.1 variants to examine its prevalence, prognostic impact, and assess its potential clinical value in limited resource settings. H3K27M mutation was detected in 28 of 105 (26.7%) samples, and its distribution was significantly associated with midline locations (p-value < 0.0001) and HGG (p-value = 0.003). Overall and event- free survival (OS and EFS, respectively) of patients with mutant tumors did not differ significantly, neither according to histologic grade (OS p-value = 0.736, EFS p-value = 0.75) nor across anatomical sites (OS p-value = 0.068, EFS p-value = 0.153). Detection of H3K27M mutation in pediatric gliomas provides more precise risk stratification compared to traditional histopathological techniques. Hence, mutation detection should be pursued in all pediatric gliomas. Meanwhile, focusing on midline LGG can be an alternative in lower-middle-income countries to maximally optimize patients’ treatment options.Amal MosaabMoatasem El-AyadiEman N. KhorshedNada AmerAmal RefaatMohamed El-BeltagyZeinab HassanSameh H. SororMohamed Saad ZaghloulShahenda El-NaggarNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-9 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Amal Mosaab Moatasem El-Ayadi Eman N. Khorshed Nada Amer Amal Refaat Mohamed El-Beltagy Zeinab Hassan Sameh H. Soror Mohamed Saad Zaghloul Shahenda El-Naggar Histone H3K27M Mutation Overrides Histological Grading in Pediatric Gliomas
description	Abstract Pediatric high-grade gliomas (HGG) are rare aggressive tumors that present a prognostic and therapeutic challenge. Diffuse midline glioma, H3K27M–mutant is a new entity introduced to HGG in the latest WHO classification. In this study we evaluated the presence of H3K27M mutation in 105 tumor samples histologically classified into low-grade gliomas (LGG) (n = 45), and HGG (n = 60). Samples were screened for the mutation in histone H3.3 and H3.1 variants to examine its prevalence, prognostic impact, and assess its potential clinical value in limited resource settings. H3K27M mutation was detected in 28 of 105 (26.7%) samples, and its distribution was significantly associated with midline locations (p-value < 0.0001) and HGG (p-value = 0.003). Overall and event- free survival (OS and EFS, respectively) of patients with mutant tumors did not differ significantly, neither according to histologic grade (OS p-value = 0.736, EFS p-value = 0.75) nor across anatomical sites (OS p-value = 0.068, EFS p-value = 0.153). Detection of H3K27M mutation in pediatric gliomas provides more precise risk stratification compared to traditional histopathological techniques. Hence, mutation detection should be pursued in all pediatric gliomas. Meanwhile, focusing on midline LGG can be an alternative in lower-middle-income countries to maximally optimize patients’ treatment options.
format	article
author	Amal Mosaab Moatasem El-Ayadi Eman N. Khorshed Nada Amer Amal Refaat Mohamed El-Beltagy Zeinab Hassan Sameh H. Soror Mohamed Saad Zaghloul Shahenda El-Naggar
author_facet	Amal Mosaab Moatasem El-Ayadi Eman N. Khorshed Nada Amer Amal Refaat Mohamed El-Beltagy Zeinab Hassan Sameh H. Soror Mohamed Saad Zaghloul Shahenda El-Naggar
author_sort	Amal Mosaab
title	Histone H3K27M Mutation Overrides Histological Grading in Pediatric Gliomas
title_short	Histone H3K27M Mutation Overrides Histological Grading in Pediatric Gliomas
title_full	Histone H3K27M Mutation Overrides Histological Grading in Pediatric Gliomas
title_fullStr	Histone H3K27M Mutation Overrides Histological Grading in Pediatric Gliomas
title_full_unstemmed	Histone H3K27M Mutation Overrides Histological Grading in Pediatric Gliomas
title_sort	histone h3k27m mutation overrides histological grading in pediatric gliomas
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/8a04d8c9e4a441e288eb794de5590171
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Histone H3K27M Mutation Overrides Histological Grading in Pediatric Gliomas

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