Abstract
Chromosomal breakpoints affecting immunoglobulin (IG) loci are recurrent in many subtypes of B-cell lymphomas. However, despite the predominant B-cell origin of the Hodgkin and Reed-Sternberg (HRS) cells in classical Hodgkin lymphoma (cHL), the presence of chromosomal translocations in IG loci has not yet been systematically explored. Therefore, we have investigated a series of cHL for chromosomal breakpoints in the IGH (n = 230), IGL (n = 139), and IGK (n = 138) loci by interphase cytogenetics. Breakpoints in the IGH, IGL, or IGK locus were observed in the HRS cells of 26 of 149 (17%), 2 of 70, and 1 of 77 evaluable cHLs, respectively. The IG partners could be identified in eight cHLs and involved chromosomal bands 2p16 (REL), 3q27 (BCL6, two cases), 8q24.1 (MYC), 14q24.3, 16p13.1, 17q12, and 19q13.2 (BCL3/RELB). In 65 of 85 (76%) cHLs evaluable for an IGH triple-color probe, the HRS cells showed evidence for a (partial) deletion of the IGH constant region, suggesting the presence of class switch recombination (CSR). Furthermore, analyses with this probe in cases with IGH breakpoints indicated that at least part of them seem to be derived from CSR defects. Our results show that chromosomal breakpoints affecting the IG loci are recurrent in cHL.
Highlights
In contrast to other B-cell malignancies, the pattern of chromosomal aberrations in classical Hodgkin lymphomaNote: Supplementary data for this article are available at Cancer Research Online.In many B-cell lymphomas, chromosomal translocations affecting the immunoglobulin heavy chain (IGH) locus in 14q32.3 are highly recurrent
For IGH, large hyperploid nuclei were detected by fluorescence in situ hybridization (FISH) in 95 of 165 (58%), whereas typical CD30-positive cells were detected by FICTION in 54 of 65 (83%), leading to a total number of 149 of 230 (65%) evaluable classical Hodgkin lymphoma (cHL)
26 (17%) cHLs displayed signal constellations pointing to chromosomal breakpoints in the IGH locus
Summary
In many B-cell lymphomas, chromosomal translocations affecting the immunoglobulin heavy chain (IGH) locus in 14q32.3 are highly recurrent. Variants of these aberrations involve the light chain n (IGK) in 2p11.2 or E (IGL) in 22q11.2. Cytogenetic studies in cHL have reported the presence of breakpoints affecting band 14q32 (containing the IGH locus) in 10% to 20% of the cases [12,13,14]. With regard to specific translocations, the only published data refer to the lack of t(14;18)(q32.3;q21.3) (IGH/BCL2 fusion) in microdissected HRS cells of cHL patients [15]. A single cHL case has been reported by FISH to carry an IGH/BCL2 fusion [16], and HRS cells from composite lymphomas have been shown
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