MET Alterations in DMGs

Diffuse midline gliomas (DMGs) are pediatric brain tumors accounting for 10-15% of all childhood brain tumors. Researchers have analyzed DMG data including data from the Pediatric Brain Tumor Atlas and found the mesenchymal-epithelial transition factor (MET) to be dysregulated in many cases of DMGs. The MET is a process by which stem cells become epithelial cells, surface cells such as cells found in the skin, organs, and vessels. The mechanisms driving MET dysregulation in these tumors remains largely unknown, but recent research is pointing towards gene fusions as a driver. Gene fusions (GFs) occur when two previously independent genes fuse. GFs have been increasingly recognized as successful targets in the treatment of many cancers, but their prevalence and therapeutic use remains understudied in DMGs. Recent findings by this research group provide a new context for studying MET biology and exploring MET gene fusions as personalized therapeutic targets in DMGs. Over the past several years, the researchers on this project have highlighted the recurrence of GFs that drive oncogenic processes in pediatric low-grade gliomas (pLGGs) and reported their potential to guide diagnosis, prognosis and/or therapy. Through better understanding of how MET biology contributes to DMGs, researchers could unlock new ways to use MET as a therapy target for the treatment of such tumors, expanding the scope of precision medicine targets in DMGs.