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• W2804588105 abstract "Somatic activating mutations of smoothened (SMO), a component of the embryonic sonic hedgehog (SHH) signaling pathway, are found in 3–5% of grade I meningiomas, most of them corresponding to meningothelial meningiomas located at the anterior skull base. By generating different developmental stage-specific conditional activations in mice, we define a restricted developmental window during which conditional activation of Smo in Prostaglandin D2-synthase-positive mesoderm-derived meningeal layer of the skull base results in meningothelial meningioma formation. We show a selective vulnerability of the arachnoid from the skull base to Smo activation to initiate tumor development. This prenatal period and specific topography are correlated to the timing and location of SHH signaling involvement in the formation of craniofacial and meninges patterning, strongly corroborating the hypothesis of a developmental origin for Smo-activated meningiomas. Finally, we provide preclinical in vitro evidence of the efficacy of the SMO-inhibitor Sonidegib, supporting further preclinical and clinical evaluation of targeted treatment for refractory SMO-mutant meningiomas." @default.
• W2804588105 created "2018-06-01" @default.
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• W2804588105 date "2018-05-22" @default.
• W2804588105 modified "2023-10-09" @default.
• W2804588105 title "Selective vulnerability of the primitive meningeal layer to prenatal Smo activation for skull base meningothelial meningioma formation" @default.
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• W2804588105 doi "https://doi.org/10.1038/s41388-018-0328-7" @default.
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