The consistent co-occurrence of somatic mutations of histone lysine modifier genes in G4 medulloblastomas that also harbor somatic chromatin variants of ZIC1 is consistent with a model in which aberrant control of the epigenome leads to ‘epigenetic instability’, with clones that by error contain ZIC1 silencing chromatin events undergoing clonal selection. This evidence concerns the gene ZIC1 and medulloblastoma.