Figure 1.
Development of CH and TMNs in patients 1 and 2. (A) The neuroblastoma treatment course for patient 1 in parallel with the emergence of CH (clone 1 in blue and clone 2 in gray) and the progression of clone 1 to t-MDS denoted in orange and red. Sequencing coverage (X) is indicated for whole-genome sequencing (WGS) and targeted sequencing (TS). For patient 1, targeted sequencing coverage is reported at the PTPN11 G503E locus. The median VAFs of mutations defining each clone are indicated as a percentage value next to their respective circle. Black circles indicate that no evidence (ie, no significant enrichment of mutant reads) of the clone in question was found at that time point. (B) The mutational spectra defining clone 2 for patient 1 (light blue and dark blue circles), clone 2 (gray circle) and t-MDS (red and orange circles) are defined by the number of single-base substitutions (SBSs, y-axis) per trinucleotide context (x-axis). SBS spectra characteristic of platinum agent-induced mutagenesis are shaded yellow. The pie charts to the right of each mutational spectra plot indicate that the majority of the SBSs at all time points are accounted for by platinum agent–associated mutational signatures (SBS31 and SBS35), with the small remainder of mutations attributed to clock-like mutational processes associated with ageing (SBS1 and SBS5) and oxidative stress (SBS18). (C) The neuroblastoma treatment timeline for patient 2 in parallel with the progression of CH (light blue circle) to AML (red circle), with persistence of residual CH after t-AML remission (dark blue circle). As in panel A, the median VAF of mutations defining each clone is indicated as a percentage value. *Treatment for t-AML before allogeneic transplant comprised cytarabine, daunorubicin, and etoposide (ADE) and fludarabine, high-dose cytarabine, idarubicin, and granulocyte colony-stimulating factor (FLAG-IDA) chemotherapy. (D) The mutational spectra defining clonal hematopoiesis and t-AML for patient 2 is shown in the same manner as that for patient 1 in panel B.

Development of CH and TMNs in patients 1 and 2. (A) The neuroblastoma treatment course for patient 1 in parallel with the emergence of CH (clone 1 in blue and clone 2 in gray) and the progression of clone 1 to t-MDS denoted in orange and red. Sequencing coverage (X) is indicated for whole-genome sequencing (WGS) and targeted sequencing (TS). For patient 1, targeted sequencing coverage is reported at the PTPN11 G503E locus. The median VAFs of mutations defining each clone are indicated as a percentage value next to their respective circle. Black circles indicate that no evidence (ie, no significant enrichment of mutant reads) of the clone in question was found at that time point. (B) The mutational spectra defining clone 2 for patient 1 (light blue and dark blue circles), clone 2 (gray circle) and t-MDS (red and orange circles) are defined by the number of single-base substitutions (SBSs, y-axis) per trinucleotide context (x-axis). SBS spectra characteristic of platinum agent-induced mutagenesis are shaded yellow. The pie charts to the right of each mutational spectra plot indicate that the majority of the SBSs at all time points are accounted for by platinum agent–associated mutational signatures (SBS31 and SBS35), with the small remainder of mutations attributed to clock-like mutational processes associated with ageing (SBS1 and SBS5) and oxidative stress (SBS18). (C) The neuroblastoma treatment timeline for patient 2 in parallel with the progression of CH (light blue circle) to AML (red circle), with persistence of residual CH after t-AML remission (dark blue circle). As in panel A, the median VAF of mutations defining each clone is indicated as a percentage value. *Treatment for t-AML before allogeneic transplant comprised cytarabine, daunorubicin, and etoposide (ADE) and fludarabine, high-dose cytarabine, idarubicin, and granulocyte colony-stimulating factor (FLAG-IDA) chemotherapy. (D) The mutational spectra defining clonal hematopoiesis and t-AML for patient 2 is shown in the same manner as that for patient 1 in panel B.

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