Fig. 4: ZIC1/ZIC4 mono-allelic and bi-allelic G3/G4 medulloblastomas enrich for distinct mutations.

a, Whisker box plot of normalized PRDM6 transcript counts in bi-allelic versus mono-allelic ZIC1/ZIC4 G4 samples. PRDM6 transcription occurs exclusively in the context of single allele inactivation of ZIC1/ZIC4. b, Oncoplot showcasing mutation status of previously published recurrently mutated genes in mono-allelic and bi-allelic G4 samples. Each column represents different samples. Each row represents different genes that are recurrently mutated in medulloblastoma. Distinct types of mutations for a gene in each patient are depicted with different size/colored bars. c, Oncoplot showcasing mutation status of previously published recurrently mutated genes in mono-allelic and bi-allelic G3 samples. d, Sample distribution summary and two-tailed Fisher’s exact test outputs for the significance of enrichment for chromatin modifier mutations in ZIC1/ZIC4 mono-allelic G4 and G3, as well as KBTBD4 mutation in ZIC1/ZIC4 bi-allelic G4. e, Summary of different proportions of G4 medulloblastoma samples exhibiting transcriptional repression within the chromatin (H3K27me3) data or RNA (mono-allelic expression) data. f, Sequencing depth normalized bigwig tracks for H3K27ac and H3K27me3 in one G4 sample with bi-allelic ZIC1/ZIC4 SE and two G4 samples with mono-allelic ZIC1/ZIC4 locus SE. Not all G4 samples with mono-allelic ZIC1/ZIC4 SE harbor H3K27me3 peak on the locus. g,h, Allelic frequencies for heterozygous SNPs in WGS, H3K27ac and H3K27me3 ChIP–seq data in the two mono-allelic G4 samples: MDT-AP-1168, where H3K27me3 is observed, and MDT-AP-2673, where H3K27me3 is absent on the ZIC1/ZIC4 locus.