American Society of Hematology

Figure 6.

$Figure 6. Genotype and clonal evolution of refractory cHL. (A) Comparison between the mutational profile of newly diagnosed cHL (n = 80; blue bars) vs refractory cHL (n = 32; red bars). Number and prevalence of mutated cases is given for each gene. (B) Venn diagram showing the number of tumor-specific mutations at baseline (light blue circle), the number of tumor-specific mutations at cHL relapse (magenta circle), and the number of tumor mutations shared between the 2 points (purple circle) in longitudinal samples from 13 patients with refractory cHL. (C) Schematic representation of mutational divergence between baseline/relapse pairs of 13 refractory cHL cases. The central node represents baseline (T1), and the distance between baseline and each refractory relapse (edge) is expressed as the fraction of unique mutations to both baseline and relapse points. (D) Phylogenetic tree describing evolutionary distances between sequential tumor pairs in a refractory cHL case. Inferred ancestral clones are also indicated. Evolutionary distance is defined as the fraction of shared mutations between tumor at the baseline and relapse time points (black node), the fraction of mutations specific for the baseline time point (red node), and the fraction of mutations specific for the relapse point (blue node). On the y-axis, 100% represents all mutations identified throughout the longitudinal course of the patient. The time between baseline and relapse is depicted on the x-axis. The leftmost node (gray circle) indicates the germline cell, and the second node from the left (black circle) indicates the last common inferable ancestral clone. The length of the branch between the germline cell and the common ancestral clone reflects the fraction of shared mutations between baseline and relapse samples. The length of the branches between the common ancestral clone and either baseline or relapse samples reflects the fractions of mutations observed only in baseline or relapse samples, respectively. The colored light blue area represents the clonal divergence between baseline and relapse points. Mutated genes shared between baseline and relapse time points (black), mutated genes specific for baseline (red), and mutated genes specific for relapse time point (blue) are annotated.$

Genotype and clonal evolution of refractory cHL. (A) Comparison between the mutational profile of newly diagnosed cHL (n = 80; blue bars) vs refractory cHL (n = 32; red bars). Number and prevalence of mutated cases is given for each gene. (B) Venn diagram showing the number of tumor-specific mutations at baseline (light blue circle), the number of tumor-specific mutations at cHL relapse (magenta circle), and the number of tumor mutations shared between the 2 points (purple circle) in longitudinal samples from 13 patients with refractory cHL. (C) Schematic representation of mutational divergence between baseline/relapse pairs of 13 refractory cHL cases. The central node represents baseline (T1), and the distance between baseline and each refractory relapse (edge) is expressed as the fraction of unique mutations to both baseline and relapse points. (D) Phylogenetic tree describing evolutionary distances between sequential tumor pairs in a refractory cHL case. Inferred ancestral clones are also indicated. Evolutionary distance is defined as the fraction of shared mutations between tumor at the baseline and relapse time points (black node), the fraction of mutations specific for the baseline time point (red node), and the fraction of mutations specific for the relapse point (blue node). On the y-axis, 100% represents all mutations identified throughout the longitudinal course of the patient. The time between baseline and relapse is depicted on the x-axis. The leftmost node (gray circle) indicates the germline cell, and the second node from the left (black circle) indicates the last common inferable ancestral clone. The length of the branch between the germline cell and the common ancestral clone reflects the fraction of shared mutations between baseline and relapse samples. The length of the branches between the common ancestral clone and either baseline or relapse samples reflects the fractions of mutations observed only in baseline or relapse samples, respectively. The colored light blue area represents the clonal divergence between baseline and relapse points. Mutated genes shared between baseline and relapse time points (black), mutated genes specific for baseline (red), and mutated genes specific for relapse time point (blue) are annotated.

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