MNGO-08. TRANSCRIPTIONAL CHARACTERIZATION OF MENINGIOMA PROGRESSION

Meningiomas are the most common adult primary tumors in the nervous system, accounting for more than 30% of all brain tumors. Meningiomas arise from arachnoid cells and while the majority is benign (WHO Grade I), about 20% (WHO Grades II and III) are considered aggressive. Grade II and III tumors are heterogeneous and present characteristics of aggressiveness including proliferation, brain invasion and increased risk of recurrence. In rare cases grades II and III meningiomas develop in the setting of a prior lower grade meningioma. Mechanisms leading to tumor progression or implicated in de novo grade II and III meningiomas are poorly understood. RNAseq was used to profile the transcriptome of grade I, II and III meningiomas (total 26 samples: 9 grade I, 11 grade II and 6 grade III) and to identify genes and pathways that may be involved in meningioma genesis and progression. Three of the grade I tumors showed progression and the resulting grade II tumors were also analyzed for distinct signature patterns. In addition, our study included meningiomas with (n=9) or without (n=12) brain invasion. Following bioinformatic analyses, including hierarchical cluster analysis and Gene Set Enrichment Analysis (GSEA) of the RNAseq data, our data demonstrate that each meningioma grade and each invasion status may be identified by specific gene expression programs. In addition, the RNAseq data was used to detect mutations not only in known genes associated with meningioma development such as NF2 or SMO but also in novel potential regulators of meningioma progression.