Evolutionary history of malignancies exposed to chemotherapy. (A) Absolute timing estimates of large chromosomal gain acquisition in 2 platinum-exposed MM with 95% confidence intervals. Multigain events for MM were timed with 2 orthogonal techniques (supplemental methods): one using SBS5-based molecular time (ie, multigain mol time) and the other using the individual SBS5 mutational rate per year estimated by a linear mixed effect model (ie, multigain corrected rate). Platinum was administered directly after the diagnosis of the primary tumor. (B) Reconstruction of tumor evolution in selected WGS cases using antecedent CH, molecular time, and duplicated chemotherapy mutation data for tMN and MM (under dotted line).