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Medulloblastoma

Medulloblastoma is the most common embryonal CNS tumor of childhood and is likely composed of biologically different subsets of tumors arising from stem and/or progenitor cells of the cerebellum. Recently, four distinct molecular subgroups of medulloblastoma have been identified [WNT (wingless), SHH (sonic hedgehog), Group 3, and Group 4]. Nearly all (90 %) of WNT patients have somatic missense mutations in CTNNB1 which promote protein stabilization. Alterations in SHH subgroup most often fall within the Shh signalling pathway. The most common are somatic or germline inactivating alterations or loss of PTCH1 and SUFU, or somatic missense mutations activating SMO. Group 3 tumors are characterized by MYC amplification resulting in high MYC mRNA expression levels compared with SHH and Group 4 tumors.The most frequently mutated somatic gene in Group 4 medulloblastoma is KDM6A, a histone H3 Lys27 (H3K27) demethylase.



Drug: Carmustine 

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