Human ganglioglioma BRAFV600E negative

Gangliogliomas (GGs) are glioneuronal tumors typically associated with a favorable prognosis and represent the most frequent neoplastic cause of long-standing drug-resistant epilepsy. While a significant proportion of GGs harbor the BRAFV600E mutation, some tumors that fulfill the neuropathological criteria for GGs do not carry this alteration. The molecular characteristics of these BRAFV600E-negative GGs remain poorly understood. In this study, we investigated their cellular and molecular landscape using single-cell transcriptomics. Our findings reveal a distinct molecular signature specifically in excitatory neurons, distinct from inhibitory neurons, astrocytes, or oligodendrocytes, in BRAFV600E-negative GGs. Notably, we identified a population of immature excitatory neurons with elevated expression of glutamatergic transmission genes, alongside highly metabolically active astrocytes and oligodendrocytes, all of which may play a role in promoting epileptic activity. This work offers a valuable foundation for further exploration of BRAFV600E-negative GGs and may inform the development of more targeted therapeutic strategies for epilepsy.