Fig. 1. Increased mutation load and clonal evolution during the myeloma disease course.

A Increase in number of mutations in samples taken at PD. There was a particular increase in patients that had received HDM (*p < 0.05, Kruskal–Wallis test). D diagnosis (start of treatment), PD: progressive disease, HDM: high-dose melphalan. For Diagnosis-PD pairs the first available PD sample was used in the analysis. B Alternating dominance in myeloma clones harboring RAS mutations. In all 7 patients with decreased clonal fraction of mutated KRAS/NRAS genes, another NRAS/KRAS mutation appeared. C Overview of treatment and M component in patient 15. Below is shown the estimated clonal composition from the DPclust analysis. The patient had a RAS shift. Also see Table S5 and Fig S3. CCF Cancer Cell Fraction, M Melphalan, R Revlimid, V Velcade, C Cyclophosphamide, Pom Pomalidomide, P Prednisolon, D Dexamethasone.