Fig. 3: Profiling of pre-treatment samples by CAPP-Seq.

A A bar plot depicting the number of SNVs detected from genotyping samples (bone marrow aspirate, n = 20; or plasma, “cfDNA”, n = 44). The number of non-coding single-nucleotide variants (SNVs), inclusive of immunoglobulin (Ig) loci, are shown in aqua; the number of coding SNVs not including Ig loci are shown in red. B A pie-chart showing the breakdown of a total of 5145 SNVs detected in Fig. 3A. IGH immunoglobulin heavy chain, IGK immunoglobulin kappa light chain, IGL immunoglobulin lambda light chain. C A bar plot showing the mutational signatures of frequently detected intronic genes (BCL7A, BCL6, LPP/BCL6 super-enhancer region), immunoglobulin loci, and intergenic regions as compared to frequently detected coding mutations in driver genes (KRAS, NRAS, TP53). SBS37, 39, 84, and 85 are highlighted as being associated with AID activity. D An example of tracking coding and non-coding mutations for disease monitoring in a case. Red arrows point to timepoints when coding genes became undetectable but non-coding regions and immunoglobulin loci remained detectable. E An oncoprint showing the coding mutations detected in our cohort (n = 64). Only coding SNVs detected in at least two patients are shown. MGUS/SMM vs MM is identified by the color bar at the bottom. MAPK, mitogen-activated protein kinase; NF-κB, nuclear factor-κB. Source data are provided as a Source Data file. F Venn diagram showing concordance of single nucleotide variants detected from bone marrow (BM) and plasma across 22 paired samples.