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.

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.


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

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