Activated signaling pathways and metabolic processes in disseminating myxoid glioneuronal tumors

Myxoid glioneuronal tumor (MGNT) is a recently recognized rare neural tumor in the 2021 WHO Classification of CNS Tumors. Myxoid glioneuronal tumor has low-grade histology and a generally good overall survival rate. However, some tumors exhibit leptomeningeal or intraventricular dissemination at presentation or during disease progression and the underlying biology is unknown. Finding activated signaling pathways and metabolic processes in disseminating MGNTs may reveal potential therapy targets for disseminated tumors. We compared the DNA methylome and transcriptome of disseminating (n = 4) and non-disseminating (n = 7) MGNTs to identify differentially methylated regions and differentially expressed genes. Gene set enrichment analysis (GSEA) was used to identify associated specific signaling and metabolic pathway activation. Myxoid glioneuronal tumors showed similar DNA methylome profiles regardless of dissemination status. Transcription factor MSX1 activation was found in disseminating MGNTs at the transcriptome level. Gene set enrichment analysis revealed the activation of the MAPK, PI3K/AKT/mTOR, MYC, and RAS pathways, as well as multiple metabolic pathways, including OXPHOS, translation, and cell cycle pathways, in disseminating MGNTs. In summary, disseminating MGNT shows simultaneous activation of multiple signaling and metabolic pathways, which may serve as potential therapeutic targets for disseminated disease.