MODL-36. EXPRESSION OF YAP1-MAML2 AND CONSTITUTIVELY ACTIVE YAP1 DRIVE THE FORMATION OF MENINGIOMA-LIKE TUMORS IN MICE THAT RESEMBLE NF2-MUTANT MENINGIOMAS

Abstract YAP1 is a transcriptional co-activator and oncogene under the control of Hippo Signaling Pathway. Functional inactivation Pathway tumor suppressors, including NF2, are frequent events in human cancers. Meningiomas most common primary brain tumors, large percentage exhibit heterozygous loss chromosome 22 (harboring NF2 gene) functional remaining gene copy, implicating oncogenic YAP activity pathobiology almost half these tumors. An alternate type activating mutation fusions that have been identified several cancer subtypes. Recently, between MAML2 subset pediatric NF2-wild meningiomas. Here, we show expression profile YAP1-MAML2-positive meningiomas resembles NF2-mutant based on global YAP-related signatures. We then use RCAS/tv-a system for postnatal transfer intracranial YAP1-MAML2 neonatal mice results formation meningioma-like tumors exert similar pattern as seen fusion-positive regulate classical target genes. demonstrate exerts resistant to inhibitory pathway signaling relies interaction with TEAD transcription factors. Pharmacological disruption this sufficient inhibit viability YAP1-MAML2-expressing mouse ex vivo. Finally, constitutively active (S127/397A-YAP1) also cause suggesting component fusion critical driver In summary, our implicate meningiomas, which mimic highlight TEAD-dependent potential therapeutic