Abstract
Paediatric oncogenesis is tightly intertwined with errors in developmental processes involving cell specification and differentiation, which are governed by intricate temporal epigenetic signals. As paediatric cancers are characterised by a low number of somatic mutations, dysregulated chromatin landscapes are believed to be key drivers of oncogenesis. Epigenetic dysregulation is induced by mutations and aberrant expression of histones and epigenetic regulatory genes, to altered DNA methylation patterns and dysregulated noncoding RNA expression. In this review, we discuss epigenetic alterations in paediatric cancer oncogenesis and recurrence, and their potential as diagnostic biomarkers. We also discuss various epigenetic drugs that have entered clinical trials for aggressive paediatric cancers. Targeting paediatric-specific epigenetic vulnerabilities may improve recurrence-free survival in high-risk cancers.
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Fig. 1: Common histone mutations in paediatric cancers.
Fig. 2: SWI/SNF complexes and their antagonistic relationship with PRC2.
Fig. 3: Schematic of miRNAs, lncRNAs, and circRNAs in paediatric oncogenesis.
Fig. 4: Epigenetic mechanisms involved in drug resistance of paediatric cancers.
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Acknowledgements
RT is supported by the National Medical Research Council grant MOH-001389-00 and Ministry of Education grant MOE-T2EP30222-0014. JYL is supported by Agency for Science, Technology and Research (A*STAR) scholarship. Figures were created with BioRender.com.
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Department of Physiology, Healthy Longevity and NUS Centre for Cancer Research Translation Research Program, Yong Loo Lin School of Medicine, National University of Singapore (NUS), 2 Medical Drive, MD9, Singapore, 117593, Republic of Singapore
Jia Yu Leung, Hsin Yao Chiu & Reshma Taneja
Laboratory of NFκB Signalling, Institute of Molecular and Cell Biology (IMCB), Agency for Science, Technology and Research (A*STAR), 61 Biopolis Drive, Proteos, Singapore, 138673, Republic of Singapore
Jia Yu Leung
Department of Pathology, Yong Loo Lin School of Medicine, National University of Singapore (NUS), National University Hospital (NUH), 5 Lower Kent Ridge Road, Singapore, 119074, Republic of Singapore
Jia Yu Leung
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JYL wrote the review and made the figures. HYC wrote the review and made the figures. RT edited the original and revised versions of the review. The review was approved by all authors.
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Leung, J.Y., Chiu, H.Y. & Taneja, R. Role of epigenetics in paediatric cancer pathogenesis & drug resistance. Br J Cancer (2025). https://doi.org/10.1038/s41416-025-02961-2
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Received:28 October 2024
Revised:22 January 2025
Accepted:10 February 2025
Published:07 March 2025
DOI:https://doi.org/10.1038/s41416-025-02961-2
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