(a) Contribution of treatment-associated signatures and aging signature to the mutational burden of metastatic tumors. The duration of the period of exposure is taken from the average duration of courses of treatment indicated in clinical guidelines (Supplementary Table 2).
(b) Contribution of treatment-associated signatures and aging signature to the mutational burden of metastatic tumors. Only tumors from patients whose treatment duration is not estimated by clinicians, but rather exactly recorded in charts are included.
(c) Risk of mutations affecting cancer genes (CGC) across tumors contributed by different signatures according to the duration of the exposure of tumors.
(d) Risk of coding-affecting mutations contributed by treatment-associated and aging signatures. Vertical lines intersecting the risk value ranges are placed at the average duration of courses of treatment indicated in clinical guidelines (Supplementary Table 2).
(e, f) Risk of coding-affecting mutations (e) and mutations affecting cancer genes (f) by treatment-associated and aging signatures. Vertical lines intersect the risk value ranges are placed at the average duration of courses of treatment of the subset of patients that were not estimated by clinicians, but rather exactly recorded in charts.