Novel insights on genetics and epigenetics as clinical targets for paediatric astrocytoma

Author:

Johns Dona A.1,Williams Richard J.123,Smith Craig M.12,Nadaminti Pavani P.4,Samarasinghe Rasika M.12ORCID

Affiliation:

1. School of Medicine, Deakin University Geelong Victoria Australia

2. Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University Geelong Victoria Australia

3. The Graeme Clark Institute, The University of Melbourne Melbourne VIC Australia

4. School of Agriculture, Food and Ecosystem Sciences, Faculty of Science, The University of Melbourne, Parkville Melbourne Victoria Australia

Abstract

AbstractPaediatric and adult astrocytomas are notably different, where clinical treatments used for adults are not as effective on children with the same form of cancer and these treatments lead to adverse long‐term health concerns. Integrative omics‐based studies have shown the pathology and fundamental molecular characteristics differ significantly and cannot be extrapolated from the more widely studied adult disease. Recent clinical advances in our understanding of paediatric astrocytomas, with the aid of next‐generation sequencing and epigenome‐wide profiling, have led to the identification of key canonical mutations that vary based on the tumour location and age of onset. These driver mutations, in particular the identification of the recurrent histone H3 mutations in high‐grade tumours, have confirmed the important role epigenetic dysregulations play in cancer progression. This review summarises the current updates of the classification, epidemiology, pathogenesis and clinical management of paediatric astrocytoma based on their grades and the ongoing clinical trials. It also provides novel insights on genetic and epigenetic alterations as diagnostic biomarkers, highlighting the potential of targeting these pathways as therapeutics for this devastating childhood cancer.

Publisher

Wiley

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