Fig. 3: Age-associated genetic alterations.

a Mutual exclusivity and co-occurrence in diagnosis samples with WGS (n = 182). When two alterations co-occurred in a sample, the alterations were excluded from analysis if the two alterations were joined by an SV (non-independent). P values are by two-sided Fisher’s exact test. Asterisk, female with ATRX and MYCN alterations. Gold, significant co-occurrence; purple, mutually exclusivity. Circle size is inversely related to P value. Gains and deletions (del) include segmental chromosome alterations and exclude whole-chromosome alterations. b Boxplot showing coding mutation burden, including 662 diagnosis samples with WGS or WES; a single outlier in group B had 200 mutations (sample numbers: group A, 197; B, 313; and C, 152). Box, interquartile range (25th to 75th percentile); middle bar, median. Whiskers are described in R boxplot documentation (a 1.5 × interquartile range rule is used). Each point represents one sample and P values are by two-sided Wilcoxon rank-sum test. c Percentage of diagnosis samples with indicated gene alterations by age group; n = 662, 182, or 499 for MYCN (WGS or WES samples), TERT (WGS samples), or ATRX (WGS samples or WES samples with ATRX targeted sequencing), respectively. P values are by two-sided Fisher’s exact test comparing prevalence among age groups. d Empirical cumulative distribution function showing diagnosis age (x-axis) of patients with alterations in MYCN (gold), TERT (blue), ATRX (red), or none of these alterations (gray, other). Five patients with both MYCN and TERT alterations and one with both MYCN and ATRX were included in the other group. 662 diagnosis samples with WGS or WES were analyzed. Y-axis represents the percent of patients in each group diagnosed at or before the age indicated on x-axis. P values are by two-sided Wilcoxon rank-sum test. Dotted lines indicate median age in the mutated group. Several ATRX-mutant patients were diagnosed at >15 years; hence the ATRX curve does not reach 100%. If only WGS data were considered, the MYCN median age was 2.5, the TERT and ATRX median ages did not change, and the P value comparisons shown were P < 0.003. Source data are provided as a Source Data file.