Figure 1. Tetraploidy is a frequent early event in MB tumourigenesis, and mutation rates vary with age and subgroup.
a, Distributions of genome-wide somatic mutation allele frequencies (the proportion of sequence reads supporting a mutation) for diploid tumours (with a peak at ~50% for heterozygous events, n=7) and tetraploid cases (with a peak at ~25%, n=7). Insets show centromeric FISH for chromosomes 1 (red) and 11 (green), confirming the predicted ploidy status.
b, Top left: Rescaled tumour:germline coverage ratio, indicating copy-number gains (red) or losses (green). Bottom left: B-Allele frequency (BAF) in the tumour at SNP positions which are heterozygous in the germline. Right: Genome alteration print (GAP) of segmented copy number and allele frequency profiles. Chromosomes with predicted 3:0/2:1/3:2 allele ratios show a BAF of ~0/0.33/0.4 and coverage ratios of ~0.75/0.75/1.25. Due to random sampling, the 2:2 allele ratio is slightly below 0.5.
c, Genome-wide somatic mutation rates are positively correlated with patient age (n=39).
d, Distribution of somatic mutation rates by tumour subgroup (n=39). p-values are according to a Wilcoxon rank-sum test with Bonferroni correction. SHH-p53: SHH-subgroup tumours harbouring a somatic or germline TP53 mutation.