ctDNA mirrors the genetics of cHL. (A) Prevalence of nonsynonymous somatic mutations discovered in ctDNA of 15 cHL cases provided with HRS cells microdissected from the paired biopsy. The graph below shows the number and type of nonsynonymous somatic mutations identified in each gene. (B) The position and type of nonsynonymous somatic mutations identified by ctDNA genotyping of the most frequently mutated genes are reported at the top of the proteins. The position and type of nonsynonymous somatic mutations that have been detected in the tumor gDNA of published cHL series¹⁹  (ITPKB and TNFAIP3) or B-cell lymphomas of the COSMIC database (version 81; STAT6) are reported at the bottom of the protein. Shapes indicate the type of the mutations, whereas color codes indicate whether they have been identified in the paired microdissected HRS cells (red) or they lacked in the paired microdissected HRS cells (gray). (C) Number of mutations in a given tumor discovered in plasma ctDNA and/or tumor gDNA. Mutations are color coded if they were identified in both plasma ctDNA and tumor gDNA (red), only in plasma ctDNA (blue), or only in tumor gDNA (gray). (D) Venn diagram summarizing the overall number of mutations discovered in both plasma ctDNA and tumor gDNA (red), only in plasma ctDNA (blue), or only in tumor gDNA (gray). The corresponding overall sensitivity of plasma cfDNA genotyping in discovering biopsy-confirmed mutations is shown. (E) For each patient, the fraction of tumor biopsy-confirmed mutations that were detected in plasma ctDNA is shown. Patients are ordered by decreasing detection rates. The red portion of the bars marks the prevalence of tumor biopsy-confirmed mutations that were detected in plasma ctDNA. The gray portion of the bars marks the prevalence of tumor biopsy-confirmed mutations that were not detected in plasma ctDNA.