While a plurality of G4 medulloblastomas alter activity of ZIC1 through genetic mutation, an additional nonoverlapping cohort (Supplementary Table 1) of G4 tumors reduce ZIC1/ZIC4 expression through uni-allelic chromatin variant repression mediated by H3K27me3 deposition, suggesting a convergence of mechanisms underlying ZIC1 alteration and that ZIC1 might be a LOF driver gene in G4 medulloblastoma. The gene discussed is ZIC1; the disease is medulloblastoma.