Glioma Group

The Jones laboratory is primarily focused on high grade gliomas which arise in children, either supratentorially, or within the brainstem. These tumours appear to have key biological and clinical distinctions, both to each other, and histologically similar lesions in adults.

To this end we have current projects focussed on:

• Genomic and epigenomic profiling of glial tumours of childhood, including large retrospective studies, prospective clinical trial cohorts, and rare entities such as infant glioma and gliomatosis cerebri
• Model development and preclinical screening of paediatric glioma subgroups, with specific projects focussing on the development of novel therapies directed against ACVR1, histone H3.3 G34R/V and ATRX mutations
• Intratumoral heterogeneity and subclonal co-operation between distinct cancer stem cell subpopulations, with a view to using disruption of these interactions as a novel area for therapeutic intervention

High-grade gliomas in children share similar histopathological features and a dismal prognosis to those that arise in adults, with a median survival of 15-18 months for cerebral hemispheric tumours and 9-12 months for diffuse intrinsic pontine glioma (DIPG).

Bulk tumour molecular profiling has recently provided important insights into the biological differences associated with high grade gliomas arising at different ages and in different locations.

We and others have identified unique genetic drivers of paediatric high-grade glioma, not present in the adult disease, which illustrate previously unappreciated connections between chromatin regulation, developmental signalling and cancer.

Distinct anatomical distributions of childhood tumours marked by these specific driver mutations points at important differences in the selective pressures vary between regions of the developing brain.

One of the primary goals of my laboratory is to better understand the function of these genetic alterations in the context of paediatric gliomagenesis and to use this mechanistic insight to develop novel therapies for children with these tumours.