Fig. 2

Comparison of whole-exome sequencing of cfDNA to whole-exome sequencing of matched tumor biopsies. a Fraction of clonal (≥0.9 cancer cell fraction, CCF) and subclonal (<0.9 CCF) SSNVs detected by MuTect in WES of tumor biopsies and confirmed (i.e., supported by ≥3 variant reads) in WES of cfDNA. Sites with <3 reads that had power <0.9 for mutation calling were not included when computing the fraction of SNVs confirmed (“Methods”). b Fraction of clonal and subclonal SSNVs detected in WES of cfDNA and confirmed in WES of tumor biopsies. For 18 patients with WES of cfDNA at a second time point t ₂, SSNVs not detected in the matched tumor biopsy but confirmed at t ₂ are indicated with black. c Analysis of clonal dynamics in an ER+ breast cancer patient diagnosed with metastatic disease 1.5 years (yrs) prior to biopsy and cfDNA collection (t ₁, Day 0). Clustering analysis of CCF for SSNVs between matched tumor biopsy and cfDNA (t ₁) is shown in the left panel. The right panel shows the CCF of four mutation clusters, one containing ESR1 L536P (Subclonal Cluster 1, orange) and the other containing ESR1 D538G (Subclonal Cluster 2, light blue), at t ₁ and t ₂ (51 days apart) from a patient with ER+ metastatic breast cancer being treated with a SERD. The lymph node biopsy was taken at the same time as cfDNA t ₁. Mutations were clustered by the CCFs for each pair of samples using Phylogic³⁹ (“Methods”). Error bars represent the 95% credible interval of the joint posterior density of the clusters. Mutations, excluding indels, having ≥90% estimated power based on coverage in both samples are shown; clusters with fewer than three mutations are excluded. The number of mutations in each cluster is indicated in the legend in parentheses