De novo germline and somatic mutations in CH, TMNs, and solid tumors in childhood cancer patients. (A) The VAF distribution (upper plot) and single nucleotide variant (SNV) burden (lower plot) of de novo germline mutations, solid tumors, CH, and TMNs in 20 pediatric oncology patients. Samples are grouped by individual. The patient’s solid tumor diagnosis is indicated in the upper left corner of the respective bar plot. Asterisks denote patients who had been exposed to platinum chemotherapy at the time of sampling. (B) Mutational signature profile of de novo germline, CH, TMN, and solid tumor mutation for the 3 individuals with clonal hematopoiesis, which demonstrates the preponderance of platinum-agent mutational signatures SBS31 and SBS35 in CH and TMN. DNM, de novo germline mutation; ES, Ewing sarcoma; IFS, infantile fibrosarcoma; Lt, left; NB, neuroblastoma; OS, osteosarcoma; RMS, rhabdomyosarcoma; Rt, right; URT, unclassifiable renal tumor; WT, Wilms tumor. Asterisk indicates previous exposure to platinum chemotherapy at the time of sampling.