Specific alterations in the BRAF gene found that may affect treatment and survival response in adult brain cancers

Researchers have identified a range of genetic alterations in glioma brain cancers that will help them to understand how different mutations in one particular gene interact with other gene alterations and which ones are more susceptible to targeted treatments in adults.

BRAF alterations are important to identify in brain tumours because they can determine treatment. However, it is unclear what types of BRAF alterations occur in adults with glioma, and whether specific BRAF alterations are associated with other gene alterations or with a different clinical course.

The term 'glioma' covers several types of tumours that originate in the glial cells in the brain. Glioblastoma is the most common type in adults and children, occurring in 3.23 per 100,000 of the population, and only 7% of glioblastoma patients survive for five years after diagnosis.New and better treatments are urgently needed, and drugs have been developed that target specific BRAF mutations, such as dabrafenib and trametinib, which inhibit the BRAFv600E mutation. Knowing which mutation or combination of genetic alterations are driving a patient's cancer is crucial to choosing the best therapy that is most likely to prolong survival.

The researchers divided the tumours into three groups, based on how the BRAF alteration activates a signalling pathway called ERK (extra-cellular signal-regulated kinase) that contributes to cancer: Class I ,Class II, Class III , and also gene rearrangements, amplifications and other, unclassified alterations.

They found that BRAF-altered gliomas in adults and children had different features. There were more Class I BRAFv600E alterations in adults, and more BRAF fusions in childhood glioma . BRAFv600E alterations were associated with improved overall survival in adults with glioma, but for the most aggressive type of glioma - glioblastoma - that improvement disappeared, and increased age was associated with worse survival in these patients.

The researchers also found that BRAFv600E conferred sensitivity to targeted therapy in adult patients.

Reference:

Dr Karisa Schreck et al,Integrated molecular and clinical analysis of BRAF-mutant glioma in adults,MEETING 34th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics