Long-term epilepsy-associated tumors: transcriptional signatures reflect clinical course.
Delev D, Daka K, Heynckes S, Gaebelein A, Franco P, Pfeifer D, Prinz M, Schnell O, Urbach H, Mader I, Beck J, Grote A, Becker AJ, Heiland DH.
Long-term epilepsy-associated tumors (LEATs) represent mostly benign brain tumors associated with drug-resistant epilepsy. The aim of the study was to investigate the specific transcriptional signatures of those tumors and characterize their underlying oncogenic drivers. A cluster analysis of 65 transcriptome profiles from three independent datasets resulted in four distinct transcriptional subgroups. The first subgroup revealed transcriptional activation of STAT3 and TGF-signaling pathways and contained predominantly dysembryoplastic neuroepithelial tumors (DNTs). The second subgroup was characterized by alterations in the MAPK-pathway and up-stream cascades including FGFR and EGFR-mediated signaling. Transcriptional activation of MAPK-pathway and BRAFV600E mutation are associated with an increased risk for tumor recurrence and malignant progression, therefore the treatment of these tumors should integrate both epileptological and oncological aspects.
