Figure 4.
Breakpoint-spanning read clouds allow for identification and reconstruction of IGH translocation events. (A) Total number of SVs involving different chromosomes identified in HRD and non-HRD MM. (B) Number of SVs involving different chromosomes in HRD (left) and non-HRD MM (right). (C) Heat maps displaying the number of read clouds shared between the IGH locus (chromosome 14 [chr14]) and breakpoint regions on chr4 (MMSET), chr11 (CCND1), and chr16 (MAF). The connected green and orange arrows schematically indicate the areas joined by the translocations. The type of SV is indicated next to the read-cloud clusters. Figure 3 and supplemental Figure 4 provide details on the interpretation of the read-cloud patterns. If the SV depicted is part of a more complex SV, this is indicated. The percentage of cells found by FISH to carry the indicated translocations is shown in parentheses above each heat map. Horizontal (red) and vertical (purple gray) lines mark the position of indicated genes and IGH VDJ regions, respectively. (D) Read-cloud overlap on chr11 (top left), from chr11 to chr14 (top right), and on chr14 (bottom right) in P14402_119. Track shows the H3K27Ac signal (median ± standard deviation [SD]) in t(11;14) MM. The connected green and orange lines schematically indicate the areas joined by events i to iv. (E) Schematic representation of the derivate chromosomes in P14402_119 as determined by lrWGS. t(nr), nonreciprocal translocation; t(r), reciprocal translocation; t(r)+fa, reciprocal translocation with a focal amplification of the breakpoint region.