Figure 5. Analysis of cancer phylogeny and clonal evolution.

(A) Phylogram constructed using Canopy integrating SNVs, curated copy number variations (CNVs) and indels detected through WES of tumor samples T1-10. Output from Canopy includes number of clones, clonal fractions and mutational groups (a-j) associated with each clone. Given the large number of somatic SNVs in this ultra-hypermutated cancer, downsampling of SNVs was performed in addition to following recommended parameters for Canopy tree building. Somatic SNVs not utilized by Canopy as well as indels were retroactively assigned based on VAF patterns to mutational groups a-j using a maximal likelihood model. Based on this analysis, six different clones of tumor cells were identified in this patient’s cancer. Truncal or group a mutations are common or ancestral to all clones of tumor cells. In contrast, mutations in groups b, d, f, h, and j are private to clones 1, 2, 3, 4, and 6, respectively. The length of horizontal branches in the tree is proportional to the number of mutations. (B) Stacked bar graph depicting the percentage of different clonal tumor cell populations as estimated by Canopy in each sample. T1-10 corresponds to samples listed in Table 1.