A type of brain tumour called IDH-mutant glioma is the most common brain tumour in young adults aged 20 to 40. While patients can survive for over a decade, these tumours are incurable, and require repeated surgeries and aggressive treatments. These tumours come in two forms: astrocytomas and oligodendrogliomas. Oligodendrogliomas respond better to chemotherapy and patients live longer, but we do not fully understand why.
One way in which tumour cells control what genes are turned on and off is through modification of DNAbinding proteins called histones. While most IDH-mutant tumours increase many of these modifications, a particular modification, H3K27me3, is reduced in oligodendroglioma. Unlike other tumours that show reduction, oligodendroglioma patients have a good prognosis. We think this happens because of unique genetic changes found in this tumour. These tumours are missing large portions of chromosomes 1 and 19, and we have found that this deletion reduces levels of two key proteins that control how H3K27me3 is added to histones. Our project will map how these histone modifications are different in oligodendroglioma versus astrocytoma, and how changes in specific genes on chromosome 1 act to block H3K27me3 in oligodendrogliomas and affect therapy responses.
This study could help us understand why oligodendrogliomas respond well to treatment, improve how we diagnose these tumours, and ultimately help us develop better therapies for all IDH-mutant tumour
