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Targeting the epigenome of cancer stem cells in pediatric nervous system tumors

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Abstract

Medulloblastoma, neuroblastoma, and pediatric glioma account for almost 30% of all cases of pediatric cancers. Recent evidence indicates that pediatric nervous system tumors originate from stem or progenitor cells and present a subpopulation of cells with highly tumorigenic and stem cell-like features. These cancer stem cells play a role in initiation, progression, and resistance to treatment of pediatric nervous system tumors. Histone modification, DNA methylation, chromatin remodeling, and microRNA regulation display a range of regulatory activities involved in cancer origin and progression, and cellular identity, especially those associated with stem cell features, such as self-renewal and pluripotent differentiation potential. Here, we review the contribution of different epigenetic mechanisms in pediatric nervous system tumor cancer stem cells. The choice between a differentiated and undifferentiated state can be modulated by alterations in the epigenome through the regulation of stemness genes such as CD133, SOX2, and BMI1 and the activation neuronal of differentiation markers, RBFOX3, GFAP, and S100B. Additionally, we highlighted the stage of development of epigenetic drugs and the clinical benefits and efficacy of epigenetic modulators in pediatric nervous system tumors.

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Acknowledgements

The authors would like to thank Dra. Marialva Sinigaglia her images expertise.

Funding

This article was supported by Ministry of Health/CNPq/FAPERGS PPSUS (Grant Number 21/2551–0000114-3 to L.G), the Children’s Cancer Institute (ICI), the National Council for Scientific and Technological Development (CNPq, MCTI, Brazil; grant 305647/2019-9 to R.R. and scholarship to N.H.F.), and the William Donald Nash Brain Tumour Research Fellowship, Brain Tumour Foundation of Canada (Canada; C.N.); the Swifty Foundation (Canada; C.N.).

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Authors and Affiliations

  1. Cancer and Neurobiology Laboratory, Experimental Research Center, Clinical Hospital (CPE-HCPA), Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil

    Natália Hogetop Freire, Mariane da Cunha Jaeger, Caroline Brunetto de Farias, Lauro Gregianin, André Tesainer Brunetto & Rafael Roesler

  2. Graduate Program in Cellular and Molecular Biology, Center of Biotechnology, Universidade Federal do Rio Grande do Sul (UFRGS), Av. Bento Gonçalves, 9500 (Setor IV - Campus do Vale), Porto Alegre, 91501-970, Brazil

    Natália Hogetop Freire & Rafael Roesler

  3. Children’s Cancer Institute, Porto Alegre, RS, Brazil

    Mariane da Cunha Jaeger, Caroline Brunetto de Farias & André Tesainer Brunetto

  4. The Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, ON, Canada

    Carolina Nör

  5. Developmental and Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON, Canada

    Carolina Nör

  6. Epigenica Biosciences, Canoas, RS, Brazil

    Barbara Kunzler Souza

  7. Department of Pediatrics, School of Medicine, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil

    Lauro Gregianin

  8. Pediatric Oncology Service, Clinical Hospital, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil

    Lauro Gregianin

  9. Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil

    Rafael Roesler

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All authors contributed to the study conception. Literature search and data analysis were performed by NHF and MCJ. The first draft of the manuscript was written by NHF and all authors revised and commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Freire, N.H., Jaeger, M.d., de Farias, C.B. et al. Targeting the epigenome of cancer stem cells in pediatric nervous system tumors. Mol Cell Biochem 478, 2241–2255 (2023). https://doi.org/10.1007/s11010-022-04655-2

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