NGS-based clonality analysis identifies clonally unrelated second primary cHL recurrences. (A) Representative data sets indicating NGS-based detection of IG gene rearrangements in paired diagnosis (D) and recurrence (R) tissue samples of case 4. Data of 2 IG targets (IGHD-IGHJ and IGKV-IGKJ) are shown. The specific clonotypes for the dominant clonal IG gene rearrangement are indicated in green. On the x-axis, the junction aa length is shown, and the abundancy of clonotypes is shown in percentages on the y-axis. (B) Summary of clonality assessment detecting second primary cHL in 10 patients. Two groups of clonally unrelated cases were defined, based on the detection of distinct clonal IG gene rearrangement(s) (distinct R) or clonal IG gene rearrangement(s) in 1 sample absent in the paired sample (discordant R). EBV status, cHL subtype, and time interval between the paired cHL samples are indicated. (C) Schematic overview of the clonal relationship of paired diagnosis and recurrence samples of the complete diagnosis and recurrence cHL cohort, based on IG-NGS clonality assessment.