Scientists at the University of California, San Francisco have discovered a common genetic driver of aggressive meningioma, which can help clinicians detect this dangerous cancer earlier and find new treatments for these difficult-to-treat tumors. A research team led by Dr. David Raleigh found that increased gene activity called FOXM1 seems to be responsible for the aggressive growth, and these tumors frequently relapse.
To investigate the factors that may lead to aggressive meningioma, Raleigh’s team collected 280 human meningioma samples from 1990 to 2015. Using a range of techniques, including RNA sequencing and targeted gene expression profiling, the researchers searched for links between gene activity and protein production in these tumors and patients’ clinical outcomes. Finally, a gene called FOXM1 was found to be the core of the growth of invasive meningioma, and also an indicator of the subsequent adverse clinical outcomes, including death.
The researchers also discovered a new link between the proliferation of aggressive meningiomas and the activation of intercellular signaling pathways, called Wnt, which usually plays a role in embryonic development and tissue formation. Given that the protein produced by FOXM1 can transmit signals along the Wnt pathway, the new data indicate that the cooperative work of FOXM1 and Wnt pathway may lead to the subsequent proliferation of meningiomas. Hypermethylation may be an early trigger for the formation of aggressive meningiomas.
Raleigh said that future work needs to find out which genes FOXM1 activates to drive meningioma growth, and block these targets with clinical therapies. It is hoped that there will be drugs to stop the pathogenesis of brain tumors in this pathway as soon as possible and benefit the majority of cancer patients.