Sonic hedgehog-associated medulloblastoma arising from the cochlear nuclei of the brainstem

Acta Neuropathologica
Daniel GrammelU Schüller

Abstract

Medulloblastoma is a malignant brain tumor of childhood that comprises at least four molecularly distinct subgroups. We have previously described that cerebellar granule neuron precursors may give rise to the subgroup with a molecular fingerprint of Sonic hedgehog (Shh) signaling. Other recent data indicate that precursor cells within the dorsal brain stem may serve as cellular origins for Wnt-associated medulloblastomas. To see whether Shh-associated medulloblastomas are also able to develop in the dorsal brainstem, we analyzed two lines of transgenic mice with constitutive Shh signaling in hGFAP- and Math1-positive brainstem precursor populations, respectively. Our results show that in both of these lines, medulloblastomas arise from granule neuron precursors of the cochlear nuclei, a derivative of the auditory lower rhombic lip. This region is distinct from derivatives of precerebellar lower rhombic lip where medulloblastomas arise in mice with constitutive-active Wnt signaling. With respect to their histology and the expression of appropriate markers, Shh tumors from the murine cochlear nuclei perfectly resemble human Shh-associated medulloblastomas. Moreover, we find that in a series of 63 human desmoplastic medulloblastom...Continue Reading

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