Molecular cytogenetic analyses of immunoglobulin loci in nodular lymphocyte predominant Hodgkin's lymphoma reveal a recurrent IGH-BCL6 juxtaposition

Abstract

Chromosomal translocations juxtaposing different oncogenes to the immunoglobulin (IG) loci are the hallmark of various B-cell lymphomas. Because the tumor cells in nodular lymphocyte predominant Hodgkin's lymphoma (NLPHL) are also derived from B cells, we examined whether NLPHL harbors chromosomal translocations that affect IG loci. Fluorescence in situ hybridization was applied to 24 NLPHL cases using probes flanking the IGH, IGK, and IGL loci as well as the BCL6 gene. Fourteen of these cases were additionally analyzed by combined immunofluorescence and fluorescence in situ hybridization. Chromosomal breakpoints in the IGH locus were detected in five NLPHL. All these cases also contained a BCL6 breakpoint. Triple-color interphase cytogenetics demonstrated the presence of an IGH-BCL6 juxtaposition, indicating a t(3;14)(q27;q32) in all five cases. There was no evidence for breakpoints affecting the IGK or IGL loci. Our results show that translocations juxtaposing the BCL6 oncogene next to the IGH locus are recurrent in NLPHL.

Figure 1

A: Combined immunophenotyping and FISH for the detection of CD20 and breakpoints in the IGH locus in case NP19. The CD20-positive large cell (blue) displays a split of the signals flanking the IGH locus indicating the presence of a translocation. The CD20 antigen detected with Alexa-594 (red fluorescence) is displayed in blue. B: Triple-color FISH assay for the detection of the t(3;14)(q27;q32) translocation juxtaposing the BCL6 and IGH loci (false color display) in case NP20. This probe set was made of the LSI IGH flanking probe (IGH telomeric in green and IGH centromeric in red) combined with a BCL6-spanning probe labeled in DEAC (pale blue signals). The small nucleus on the right displays the regular signal constellation: two red/green co-localizations indicating intact IGH gene and two pale blue signals pointing to intact BCL6 alleles. The large nucleus on the left shows multiple split of green and red signals indicating a breakpoint in the IGH locus. Disrupted red and green signals co-localize with pale blue BCL6 signals pointing to a t(3;14)(q27;q32) translocation involving the BCL6 and IGH loci as well as the presence of several derivative chromosomes. This signal pattern was found recurrently in this case.