A human iPS cell-based model of medulloblastoma demonstrates co-operativity between SHH signalling and mutation in an epigenetic modifier

Medulloblastoma (MB), the most common malignant pediatric brain tumor, is comprised of four subgroups (WNT, SHH, Group 3, Group 4). While recurrent single nucleotide variations is rare in MB, mutation of epigenetic modifiers is frequent, suggesting a mechanism for tumorigenesis. Genetically engineered mouse models (GEMMs) recapitulate some aspects of MB, but fail to replicate the epigenetics characteristic of human MB. Therefore, we aimed to develop the first human stem cell based model of MB using iPSC derived from Gorlin syndrome (GS), a disease that predisposes patients to SHH MB due to heterozygosity for PTCH1