Fig. 1. Recurrent somatic alterations by age group in neuroblastoma.

Top, age at diagnosis and number of coding mutations in each of 685 neuroblastoma samples (662 diagnosis, 23 relapse) sequenced by WGS or WES, with samples categorized into <18 months of age at diagnosis (group A, n = 206), 18 months to 5 years (group B, n = 325), and 5 or more years (group C, n = 154). Middle, segmental chromosome copy changes which were statistically significant per GISTIC analysis, and structural variants; blue indicates segmental copy loss, red indicates segmental copy gain, white indicates no change. 9+ WC gains samples (gain of nine or more whole chromosomes) are shown in dark red. Bottom, somatic variants in driver genes. Color indicates the type of mutation (key at right). Samples with more than one mutation type for a gene have multiple colors indicated. Significantly mutated genes (SMGs), as identified through MutSigCV and/or GRIN, range from MYCN at the top to ATRX at the bottom, while the remainder are known cancer genes that have pathogenic variants in our cohort but did not pass the SMG test. Barplot to the right shows percentage of samples with each gene somatically altered, and variant type indicated by color; the denominator was 685 samples for all alterations except for t(11;17), TERT, SHANK2, and PTPRD (205 samples with WGS as these variants required WGS to detect) and ATRX (522 samples including WGS samples plus WES samples with ATRX targeted sequencing allowing SV detection). Copy gains include focal MYCN amplifications with log₂ fold change of >2.0 (>8 copies); ALK copy gains meeting this criterion or one-copy ALK gains associated with a likely activating SV; or focal TERT gains of one copy or more.