Study describes new targets for precision treatment of meningiomas

Winner of the Integra Foundation Award, Mark W. Youngblood, presented his research, Clinical and Molecular Features of Genomic Subgroups in Meningioma, during the 2017 American Association of Neurological Surgeons (AANS) Annual Scientific Meeting.

The authors of this study previously described the genomic landscape of meningiomas, identifying five genomic groups, including NF2, TRAF7/KLF, TRAF7/AKT1, Hedgehog and POLR2A mutants, which explain the molecular background of over 80 percent of benign samples. The study identifies novel relationships of driver mutation with clinical and molecular characteristics and describes new targets for precision treatment of meningiomas.

Authors used next-generation genomic approaches to classify over 1,500 meningiomas, identifying known driver mutations and correlating these with clinical characteristics. In a smaller cohort, the team performed RNA- and H3K27ac ChIP-sequencing to investigate the transcriptional and epigenomic associations underlying meningioma pathogenesis.

Meningioma subgroups showed significant correlation with intracranial origin, pathologic grade and histology. The authors found NF2-mutant tumors to be enriched among the higher grade meningiomas, localizing to the convexity regions posterior to the coronal suture. By contrast, non-NF2 mutant meningiomas originated primarily from the anterior convexity and skull base regions, including midline localization of Hedgehog mutant meningiomas, which included the majority of olfactory groove and planum sphenoidale tumors. Using H3K27ac ChIP-seq data, authors found differential super-enhancer binding in each subgroup that drove expression of genes related to embryonic development of the meninges, including WNT activation in NF2 mutants, GRHL3 in KLF4-mutant samples and EGFR in Hedgehog mutant meningiomas.