lrWGS allows for reliable detection of CNVs and identification of double-hit MM. (A) Heat map showing the copy numbers across the somatic chromosomes (chr1-22) as calculated from lrWGS coverage. Copy-number was in two cases (indicated by*) corrected to the chr4 copy-number (supplemental Methods). Vertical black lines indicate genomic localization of FISH probes. Regions investigated by FISH are indicated by black dots, with the position of the dot above or below the gray line indicating copy-number gains or losses, respectively. (B) Venn diagram showing the overlap between CNVs called by FISH and by lrWGS among regions included in the FISH panel (excluding the IGH regions). Regions investigated by FISH are indicated in panel A. (C) Copy numbers of total, haplotype-specific, and unphased lrWGS coverage in the area surrounding the TP53 locus. Median copy number in the normal control samples (germ line [GL]) is shown for comparison. Vertical lines indicate the boundaries of the FISH probes used to identify chr17p CNVs. For P11603_109, the position of the acquired TP53 mutation (detected using the lrWGS data) is indicated. VAF, variant allele frequency.