Cryptic insertions of immunoglobulin light-chain enhancer regions near the CCND3 gene in 3 cyclin D1⁻MCL. (A) Circos plots with interchromosomal SVs detected by MP-WGS (black lines) and CNA detected by copy-number arrays (blue for gains and red for losses) in cases ID6 and ID3. The rearrangement between chr2 (IGK-enh) and chr6 (CCND3) in both cases is indicated with a discontinuous line. (B) Schematic representation of the 6p region around the CCND3 locus showing the location of the cryptic insertion of the IGK-enh (chr2) close to 5′ of the CCND3 gene in cases ID6 and ID3 (the length of the inserted fragments is indicated), and the location of the cryptic insertion of the IGL enhancer (chr22) near 3′ of the CCND3 gene in case ID5. The breakpoints were detected by MP-WGS (cases ID3 and ID6), and WES (case ID5), and further verified and refined to base pair resolution by Sanger sequencing in the 3 cases. There were 1-, 2-, and 3-bp homology at the breakpoint junctions, respectively. (C) Verification of the cryptic IGK/CCND3 insertion by FISH in case ID3 using the fusion probe IGK-enh (labeled in green) with CCND3 (labeled in red). FISH analysis shows 2 red and 2 green signals in normal cells and the yellow arrows highlight cells with 1 red and 1 small green signal juxtaposed, indicating the presence of the IGK insertion. Magnifications of cells with the rearrangement are shown at the right side (4′,6-diamidino-2-phenylindole [DAPI] stain; original magnification ×100). *Breakpoints estimated from MP-WGS data. enh, enhancer.