Genomic and epigenomic profiling
Having previously published some of the earliest and largest molecular profiling studies of paediatric high grade glioma and DIPG, we recently compiled a retrospective analysis of more than 1000 cases of these rare tumours.
We show that they are in fact comprised of more than 10 distinct subgroups, ranging from infant tumours driven by single gene fusion events to hypermutant cases with some of the highest mutational burdens in human cancer. Many of these tumours have key targetable alterations, whilst others remain extremely poorly defined.
We were biology leads for the prospective HERBY randomised phase II clinical trial, whereby despite the trial showing a lack of benefit with the addition of bevacizumab to standard chemoradiotherapy, we identified subgroups of tumours with MAPK activation to have a longer survival due to their enhanced immunogenic profile.
We are currently UK biology leads for the BIOMEDE stratified trial in DIPG, and are developing co-clinical trials to identify patient-specific drug targets and personalised resistence mechanisms.
Although our understanding of the biology of these tumours has improved dramatically in the past few years, there remain subgroups of the disease which remain understudied.
These include gliomatosis cerebri, an extremely infiltrative variant excluded from current clinical trials, and infant glioma, for which our collections have increased to more than 200 as we lead on international collaborations in the molecular study of these entities.