Novel insights on genetics and epigenetics as clinical targets for paediatric astrocytoma
Dona A Johns1, Richard J Williams1,2,3, Craig M Smith1,2
1School of Medicine, Deakin University, Geelong, Victoria, Australia.
Insights
Paediatric astrocytomas differ significantly from adult forms, requiring distinct treatments. Understanding genetic and epigenetic alterations is key to developing effective therapies for this childhood cancer.
Area of Science:
- Oncology
- Genetics
- Epigenetics
Background:
- Paediatric and adult astrocytomas exhibit distinct molecular and pathological characteristics.
- Treatments effective in adults are often less effective and cause adverse effects in children.
- Previous research indicates significant differences that prevent extrapolation from adult studies.
Purpose of the Study:
- To review current understanding of paediatric astrocytoma classification, epidemiology, pathogenesis, and clinical management.
- To highlight advances in identifying genetic and epigenetic alterations.
- To explore potential therapeutic targets based on these molecular findings.
Main Methods:
- Review of integrative omics-based studies.
- Analysis of next-generation sequencing and epigenome-wide profiling data.
- Summary of current clinical trial information.
Main Results:
- Identification of key driver mutations varying by tumor location and age of onset.
- Confirmation of the role of epigenetic dysregulation, particularly histone H3 mutations, in high-grade paediatric astrocytomas.
- Paediatric astrocytomas possess unique molecular drivers distinct from adult counterparts.
Conclusions:
- Paediatric astrocytomas require unique diagnostic and therapeutic strategies.
- Genetic and epigenetic alterations serve as crucial diagnostic biomarkers.
- Targeting identified molecular pathways offers promising therapeutic potential for childhood astrocytoma.
Abstract:
Paediatric 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.
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