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  • Review Article
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Paediatric and adult malignant glioma: close relatives or distant cousins?

Nature Reviews Clinical Oncology volume 9, pages 400–413 (2012)Cite this article

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Abstract

Gliomas in children differ from their adult counterparts by their distribution of histological grade, site of presentation and rate of malignant transformation. Although rare in the paediatric population, patients with high-grade gliomas have, for the most part, a comparably dismal clinical outcome to older patients with morphologically similar lesions. Molecular profiling data have begun to reveal the major genetic alterations underpinning these malignant tumours in children. Indeed, the accumulation of large datasets on adult high-grade glioma has revealed key biological differences between the adult and paediatric disease. Furthermore, subclassifications within the childhood age group can be made depending on age at diagnosis and tumour site. However, challenges remain on how to reconcile clinical data from adult patients to tailor novel treatment strategies specifically for paediatric patients.

Key Points

  • Paediatric malignant gliomas, which are classified by morphological criteria that were designed specifically for adult tumours, have long been considered to be the same as adult disease

  • Diffusely infiltrating malignant lesions arising in the ventral pons—diffuse intrinsic pontine gliomas (DIPGs)—generally occur in children, and pose unique problems in surgical management, drug delivery and biological study

  • Differences in DNA copy number and gene-expression profiles have provided evidence that paediatric high-grade glioma (HGG) and DIPG have different developmental origins and are biologically distinct from the corresponding adult tumours

  • Specific mutations at key post-translationally modified residues in histones (H3F3A and HIST1H3B) and genes involved in chromatin remodelling (ATRX–DAXX) define the paediatric diseases

  • An improved range of biologically relevant preclinical models are required to overcome clinical failures of single-targeted agents in children based on extrapolation from data from adults with HGG

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Figure 1: Objective response rates of single-agent chemotherapy trials (of carboplatin,142, 143 cisplatin,144, 145 nitrosourea,145, 146, 147, 148, 149 etoposide,150, 151, 152 ifosfamide,152, 154 irinotecan155, 156, 157, 158 and temozolomide159, 160, 161, 162, 163, 164) in adult and paediatric (including DIPG) HGG.
Figure 2: Signalling pathways and clinically relevant targeted inhibitors in pHGG and DIPG.

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Acknowledgements

C. Jones and L. Perryman acknowledge support from the Specialist Biomedical Research Centre for Cancer at The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research. D. Hargrave acknowledges support from the Great Ormond Street Hospital/Institute of Child Health, Biomedical Research Centre.

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  1. Divisions of Molecular Pathology and Cancer Therapeutics, The Institute of Cancer Research, 15 Cotswold Road, SM2 5NG, Sutton, UK

    Chris Jones

  2. Biotech Research and Innovation Centre, University of Copenhagen, Ole Maaløes Vej 5, DK-2200, Copenhagen N, Denmark

    Lara Perryman

  3. Department of Paediatric Oncology, Great Ormond Street Hospital, Great Ormond Street, WC1N 3JH, London, UK

    Darren Hargrave

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All authors researched the data and wrote the article, as well as contributed to discussions of its content and edited the manuscript before submission.

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Jones, C., Perryman, L. & Hargrave, D. Paediatric and adult malignant glioma: close relatives or distant cousins?. Nat Rev Clin Oncol 9, 400–413 (2012). https://doi.org/10.1038/nrclinonc.2012.87

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