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Embryonal tumors with multi-layered rosettes: a disease of dysregulated miRNAs

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Abstract

Introduction

ETMRs are highly lethal, pediatric embryonal brain tumors, previously classified as various histologic diagnoses including supratentorial primitive neuroectodermal tumors (sPNET) and CNS PNET. With recognition that these tumors harbor recurrent amplification of a novel oncogenic miRNA cluster on chr19, C19MC, ETMRs were designated as a distinct biological and molecular entity with a spectrum of histologic and clinical manifestations.

Methods

We reviewed published literature describing clinical presentation, the genetic and epigenetic drivers of oncogenesis, and recent therapeutic strategies adopted to combat these aggressive tumors.

Results

As a consequence of C19MC amplification, ETMRs upregulate several oncogenic and pluripotency proteins, including LIN28A, DNMT3B and MYCN, that confer a unique epigenetic signature reminiscent of nascent embryonic stem cells. In this review, we focus on the dysregulation of miRNAs in ETMR, the major pathogenic mechanism identified in this disease.

Conclusion

Despite the use of multi-modal therapeutic regimens, ETMR patients have dismal survival. Understanding the unique biology of these tumors has provided new insights towards novel therapeutic targets.

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Acknowledgements

This project was funded by a Canadian Institutes of Health Research, Grant Number 137011. AH is a Canada Research Chair in Rare Childhood Brain Tumours (Tier 1).

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Authors and Affiliations

  1. Division of Hematology-Oncology, Department of Pediatrics, The Hospital for Sick Children, University of Toronto, 555 University Ave, Toronto, ON, M5G1X8, Canada

    Nikhil Raghuram, Eric Bouffet & Annie Huang

  2. Monash Children’s Cancer Centre, Monash Children’s Hospital. Monash Health. Center for Cancer Research, Hudson Institute of Medical Research, and Department of Molecular and Translational Science, School of Medicine, Nursing and Health Science, Monash University, Clayton, VIC, 3168, Australia

    Sara Khan

  3. Division of Hematology/Oncology, Arthur and Sonia Labatt Brain Tumor Research Centre, Hospital for Sick Children, Toronto, ON, M5G0A4, Canada

    Sara Khan, Iqra Mumal & Annie Huang

  4. Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, Toronto, ON, M5S1A8, Canada

    Iqra Mumal & Annie Huang

  5. Department of Medical Biophysics, Faculty of Medicine, University of Toronto, Toronto, ON, M5G1L7, Canada

    Annie Huang

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  1. Nikhil Raghuram
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Raghuram, N., Khan, S., Mumal, I. et al. Embryonal tumors with multi-layered rosettes: a disease of dysregulated miRNAs. J Neurooncol 150, 63–73 (2020). https://doi.org/10.1007/s11060-020-03633-2

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