Epigenetic modifications and their roles in pediatric brain tumor formation: emerging insights from chromatin dysregulation

Pediatric brain tumors, the most devastating cancers affecting children, are believed to originate from neural stem/progenitor cells in developing brain. In precise timing and specific regions during the brain development, chromatin deregulation plays crucial roles in redirecting normal neuronal dif...

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Main Authors: Kento Kawata, Owen S. Chapman, Satoshi Narumi, Daisuke Kawauchi
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-06-01
Series:Frontiers in Oncology
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Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2025.1569548/full
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author Kento Kawata
Owen S. Chapman
Satoshi Narumi
Daisuke Kawauchi
author_facet Kento Kawata
Owen S. Chapman
Satoshi Narumi
Daisuke Kawauchi
author_sort Kento Kawata
collection DOAJ
description Pediatric brain tumors, the most devastating cancers affecting children, are believed to originate from neural stem/progenitor cells in developing brain. In precise timing and specific regions during the brain development, chromatin deregulation plays crucial roles in redirecting normal neuronal differentiation pathways toward tumorigenesis. Indeed, epigenomic abnormalities are thought to be more important for brain tumor formation especially in children than adults, as pediatric brain tumors generally exhibit fewer genetic mutations compared to adult brain tumors. Given the small number of mutations, targeting such limited alterations involved in cancer epigenomes is expected to be more effective in pediatric brain tumors. The mechanisms of cancer epigenomes include mutation or dysregulation of chromatin remodelers, histone modifiers, histones themselves, and DNA methylation enzymes. Furthermore, genomic rearrangements and/or higher-order chromatin topology also contribute to these epigenomic mechanisms. These mechanisms are commonly observed in various types of pediatric brain tumors. However, alterations in chromatin regulatory factors differ across tumor types, reflecting the unique epigenetic landscapes shaped by their tumor origins. Accordingly, clarifying their functional similarities and differences across tumor types could offer valuable insights for finding new therapeutic strategies. Thus, this review article focuses on elucidating how pediatric brain tumors arise from epigenomic deregulation and what epigenetic molecules or mechanisms could serve as therapeutic targets.
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spelling doaj-art-5ecfb237680149ff8a2b2dd5f311e6f32025-08-20T03:31:23ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2025-06-011510.3389/fonc.2025.15695481569548Epigenetic modifications and their roles in pediatric brain tumor formation: emerging insights from chromatin dysregulationKento Kawata0Owen S. Chapman1Satoshi Narumi2Daisuke Kawauchi3Department of Pediatrics, Keio University School of Medicine, Tokyo, JapanDepartment of Neuro-oncology, Institute of Brain Science, Graduate School of Medical Sciences, Nagoya City University, Aichi, Nagoya, JapanDepartment of Pediatrics, Keio University School of Medicine, Tokyo, JapanDepartment of Neuro-oncology, Institute of Brain Science, Graduate School of Medical Sciences, Nagoya City University, Aichi, Nagoya, JapanPediatric brain tumors, the most devastating cancers affecting children, are believed to originate from neural stem/progenitor cells in developing brain. In precise timing and specific regions during the brain development, chromatin deregulation plays crucial roles in redirecting normal neuronal differentiation pathways toward tumorigenesis. Indeed, epigenomic abnormalities are thought to be more important for brain tumor formation especially in children than adults, as pediatric brain tumors generally exhibit fewer genetic mutations compared to adult brain tumors. Given the small number of mutations, targeting such limited alterations involved in cancer epigenomes is expected to be more effective in pediatric brain tumors. The mechanisms of cancer epigenomes include mutation or dysregulation of chromatin remodelers, histone modifiers, histones themselves, and DNA methylation enzymes. Furthermore, genomic rearrangements and/or higher-order chromatin topology also contribute to these epigenomic mechanisms. These mechanisms are commonly observed in various types of pediatric brain tumors. However, alterations in chromatin regulatory factors differ across tumor types, reflecting the unique epigenetic landscapes shaped by their tumor origins. Accordingly, clarifying their functional similarities and differences across tumor types could offer valuable insights for finding new therapeutic strategies. Thus, this review article focuses on elucidating how pediatric brain tumors arise from epigenomic deregulation and what epigenetic molecules or mechanisms could serve as therapeutic targets.https://www.frontiersin.org/articles/10.3389/fonc.2025.1569548/fullpediatric brain tumorepigeneticschromatin remodelerhistone modificationgenomic rearrangementextrachromosomal DNA (ecDNA)
spellingShingle Kento Kawata
Owen S. Chapman
Satoshi Narumi
Daisuke Kawauchi
Epigenetic modifications and their roles in pediatric brain tumor formation: emerging insights from chromatin dysregulation
Frontiers in Oncology
pediatric brain tumor
epigenetics
chromatin remodeler
histone modification
genomic rearrangement
extrachromosomal DNA (ecDNA)
title Epigenetic modifications and their roles in pediatric brain tumor formation: emerging insights from chromatin dysregulation
title_full Epigenetic modifications and their roles in pediatric brain tumor formation: emerging insights from chromatin dysregulation
title_fullStr Epigenetic modifications and their roles in pediatric brain tumor formation: emerging insights from chromatin dysregulation
title_full_unstemmed Epigenetic modifications and their roles in pediatric brain tumor formation: emerging insights from chromatin dysregulation
title_short Epigenetic modifications and their roles in pediatric brain tumor formation: emerging insights from chromatin dysregulation
title_sort epigenetic modifications and their roles in pediatric brain tumor formation emerging insights from chromatin dysregulation
topic pediatric brain tumor
epigenetics
chromatin remodeler
histone modification
genomic rearrangement
extrachromosomal DNA (ecDNA)
url https://www.frontiersin.org/articles/10.3389/fonc.2025.1569548/full
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AT owenschapman epigeneticmodificationsandtheirrolesinpediatricbraintumorformationemerginginsightsfromchromatindysregulation
AT satoshinarumi epigeneticmodificationsandtheirrolesinpediatricbraintumorformationemerginginsightsfromchromatindysregulation
AT daisukekawauchi epigeneticmodificationsandtheirrolesinpediatricbraintumorformationemerginginsightsfromchromatindysregulation