Fig. 7: Genome-wide mutational burden in the context of immunotherapy.

a Distribution of coding tumor mutational burden (TMB) as assessed by WGS across the cohort (n = 114), colored by treatment status of the patient at the time of sampling. Dotted line indicates median-coding TMB (SNVs and indels) as previously reported by the Zero Childhood Cancer study. Patients are grouped by disease category (NB: neuroblastoma, CNS: central nervous system, C: carcinoma, WT: Wilms tumor, Germ: germ cell tumor, H: hepatoblastoma, O: other). Carcinoma patients C1 and C2 who responded to immunotherapy are labeled. b Distribution of structural variant (SV) (right) and gene fusion (left) burden across the samples with both WGS and RNA-seq available (n = 101). Patient C2 had a poor-quality RNA sample, so clonal fusions from another time point from the same patient are shown. c (top) Genome-wide distribution and patterns of somatic mutations for tumor C1 (H135022), patient with metastatic adrenocortical carcinoma, depicting high SV burden. Circos plots are shown as described in Fig. 6. PET imaging shows resolution of a large pulmonary metastatic lesion (red arrow) following treatment with nivolumab and ipilimumab. d Genome-wide distribution and patterns of somatic mutations for H135462, a 14-year-old with relapsed refractory poorly differentiated clear-cell carcinoma with high TMB and SV burden. Circos plots are shown as described in Fig. 5. PET imaging shows resolution of multiple metastatic lesions (red arrows) following treatment with pembrolizumab. Source data for panels a and b are provided at the data repository. Raw data for panel c, d can be accessed at the dbGAP study.