Diagrammatic representation of the novel IGH rearrangements identified with the capture/sequencing methodology. (A) IGH-IRF8 fusions were found in two DLCBL biopsies: the breakpoints on chromosome 16q24 mapped on a ∼40-kb range centromeric to the IRF8 locus, which is then translocated to the derivative chromosome 14. At the IGH locus, the breakpoints were located in the switch μ or γ regions, placing IRF8 under the control of the Eμ or Eα enhancers, respectively. (B) In the IGH-EBF1 rearrangement, the breakpoint on chromosome 5q34 mapped ∼1 kb telomeric to the EBF1 gene (transcribed from the telomere to the centromere) and was juxtaposed by a large segment of the IGH locus containing the Eμ enhancer. (C) In another DLBCL, a fusion was identified between the IGH locus and the intron 1-2 of the EIF4A1 gene, on chromosome 17p13. Three other genes, including the B-cell relevant TNFSF13 (APRIL), map immediately telomeric to the breakpoint and could also be influenced by the IGH regulatory elements; both derivative chromosomes are shown. PCR and Sanger sequencing in this case also suggested that this translocation is associated with an inversion within either chromosome 17p13 or 14q32. In each panel, the breakpoints are indicated by arrows, the genes and regulatory elements within the IGH locus are labeled, and the partner genes’ exons are numbered. Sequencing traces for each of the highlighted fusions are also shown.