MCL ctDNA signature allows discrimination from CH variants and recovery of additional reporters to support MRD^ctDNA decisions. (A) Line graph showing smoothened enrichment of mutant fragments (y-axis) according to fragment length (x-axis) and variant class or sample material (color). Note the similarity between somatic background mutations after 6 cycles and pretreatment. (B) Dot plot according to mutant and reference fragments for subnucleosomal enrichment (y-axis) of MCL reporter mutations in the pretreatment cfDNA. Each dot represents an individual reporter mutation; variants with >20 fragments for classification are included. Mann-Whitney U test P value for comparison shown. (C) Dot plot showing subnucleosomal enrichment (y-axis) for ambiguous variants detected in the pretreatment ctDNA according to gene target (x-axis). Each variant is represented by a dot; mutations with >20 fragments are shown. Variants in canonical CH genes that were detected in matched PB and/or BM sequences under CH. Other driver gene mutations and immunoglobulin mutations are shown separately. (D) Dot and line graphs showing the VAF (y-axis, logarithmic scale) of cfDNA variants at pretreatment and after 6 cycles of therapy according to their reporter and fragment pattern predicted status (color). Lines connect same variants in different time points. TP53 mutation not identified in the genotyping tumor tissue of example 1 annotated.