Figure 4. Clonal evolution of drug resistance in patients.

Clonal evolution tracking in 4 patients. a) Anatomical sites sequenced with DLP, a phylogenetic tree of the clones, then clonal fractions, mean truncal SV VAF and TP53 VAF, CA-125 and treatment history over time for patient 044. Disease recurrences are annotated on the CA-125 track. b) ERBB2 copy number in clone B vs E across cells c) Pseudobulk copy number of clones B and E at 10kb resolution in chromosomes 2 and 17. A translocation specific to clone E and implicated in the ERBB2 amplification is highlighted. Below shows the read counts of this translocation across timepoints in cfDNA d) CT scan images from day 0 and day 84 from 2 sites. Orange/white arrows indicate site of disease e) Clonal tracking in patient 009, same as panel a). f) Diagram of mutations impacting the BRCA1 gene: location of frameshift deletion shown with red dashed line, large 1.37kb deletion shown in gray. Number of reads supporting the 1.37kb deletion in cfDNA across time. g) Clonal tracking in patient 107, same as panel a). h) NOTCH3 and CCNE1 single cell copy number distribution across clones i) Clonal tracking in patient 045, same as panel a). j) RAB25 and CCNE1 single cell copy number distribution across clones