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Medulloblastoma epigenetics and the path to clinical innovation

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Abstract

Introduction

In the last decade, a number of genomic and pharmacological studies have demonstrated the importance of epigenetic dysregulation in medulloblastoma initiation and progression. High throughput approaches including gene expression array, next-generation sequencing (NGS), and methylation profiling have now clearly identified at least four molecular subgroups within medulloblastoma, each with distinct clinical and prognostic characteristics. These studies have clearly shown that despite the overall paucity of mutations, clinically relevant events do occur within the cellular epigenetic machinery. Thus, this review aims to provide an overview of our current understanding of the spectrum of epi-oncogenetic perturbations in medulloblastoma.

Methods

Comprehensive review of epigenetic profiles of different subgroups of medulloblastoma in the context of molecular features.

Summary

Epigenetic regulation is mediated mainly by DNA methylation, histone modifications and microRNAs (miRNA). Importantly, epigenetic mis-events are reversible and have immense therapeutic potential.

Conclusion

The widespread epigenetic alterations present in these tumors has generated intense interest in their use as therapeutic targets. We provide an assessment of the progress that has been made towards the development of molecular subtypes-targeted therapies and the current status of clinical trials that have leveraged these recent advances.

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Acknowledgements

Work in VG Lab is supported by Grants from the National Institutes of Health (R01NS079715 and R03NS077021), Cancer Prevention Research Institute of Texas (CPRIT-RP150301), Rally Foundation for Childhood Cancers, and Addis Faith Foundation.

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  1. Amanda R. Haltom and Stephanie A. Toll have contributed equally to this work.

Authors and Affiliations

  1. Division of Pediatrics, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA

    Amanda R. Haltom, Donghang Cheng, Shinji Maegawa, Vidya Gopalakrishnan & Soumen Khatua

  2. Division of Pediatric Hematology/Oncology, Department of Pediatrics, Children’s Hospital of Michigan, Detroit, USA

    Stephanie A. Toll

  3. Department of Molecular and Cellular Oncology, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA

    Vidya Gopalakrishnan

  4. Center for Cancer Epigenetics, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA

    Amanda R. Haltom, Donghang Cheng, Shinji Maegawa & Vidya Gopalakrishnan

  5. Brain Tumor Center, The University of Texas, MD Anderson Cancer Center, Houston, TX, USA

    Vidya Gopalakrishnan & Soumen Khatua

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Haltom, A.R., Toll, S.A., Cheng, D. et al. Medulloblastoma epigenetics and the path to clinical innovation. J Neurooncol 150, 35–46 (2020). https://doi.org/10.1007/s11060-020-03591-9

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