(a) Pie chart showing the molecular subgroup distribution within the combined discovery cohort of the three medulloblastoma sequencing studies (n=189)^-. (b) Venn diagram showing the number of mutated genes identified in the three next-generation sequencing studies of medulloblastoma (discovery cohorts, n=189) detailed in the text and the degree of overlap between them. Fifteen genes were commonly mutated in all three studies. (c) Frequency (%) and distribution of top candidate genes subject to recurrent non-synomonous mutation (SNV/indel) in medulloblastoma subgroups. Frequency is expressed as the percentage of affected cases within each subgroup and the denominator was dependent on the total number of cases screened for each individual gene (since not all genes were included in the targeted replication cohorts). Genes highlighted in bold were found to be mutated in each of the three sequencing studies. (d) Oncoprints showing the frequency and sample distribution of the most prevalent somatic mutations (SNVs/indels) and focal SCNAs within the medulloblastoma subgroups as determined in the four genomic studies described in the text^-, .

Schematic representations of the most frequently targeted, novel candidate genes in medulloblastoma. Mutation positions are based on the three next-generation sequencing studies described in the text^-. Genes are depicted within the subgroup for which they show the greatest enrichment. In Group 3, the zoom box adjacent to MYC depicts the general structure of the recurrent PVT1-MYC fusion genes reported by Northcott et al. In Group 4, the zoom box adjacent to SNCAIP illustrates the general structure of the SNCAIP tandem duplications described by Northcott et al. Abbreviations: DEAD, DEAD domain; LIM, LIM domain; ANK, ankyrin repeat; HLH, helix-loop-helix domain; NIF, NLI interacting factor-like phosphatase; TPR, tetratricopeptide repeat; JmjC, Jumonji C domain; InDel, insertion/deletion.

Cartoon summarizing a selection of genes recurrently mutated and/or undergoing SCNA in medulloblastoma that are functionally associated with chromatin regulation. Both inactive heterochromatin and active euchromatin and the typical histone marks associated with these chromatin states are illustrated.

Distribution of prevalent broad SCNAs and recurrent mutations (SNVs/indels) in Group 3 and 4 medulloblastomas. The majority of both Group 3 and Group 4 medulloblastomas are devoid of somatic mutations in any of the most recurrently mutated genes within these subgroups.