Chromosomal breakpoints affecting immunoglobulin loci are recurrent in Hodgkin and Reed-Sternberg cells of classical Hodgkin lymphoma.
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.
Martín-Subero
José I
JI
Institutes of Human Genetics and Hematopathology, University Hospital Schleswig-Holstein Campus Kiel, Kiel, Germany.
Klapper
Wolfram
W
Sotnikova
Anna
A
Callet-Bauchu
Evelyne
E
Harder
Lana
L
Bastard
Christian
C
Schmitz
Roland
R
Grohmann
Susanne
S
Höppner
Jorge
J
Riemke
Jennifer
J
Barth
Thomas F E
TF
Berger
Françoise
F
Bernd
Heinz-Wolfram
HW
Claviez
Alexander
A
Gesk
Stefan
S
Frank
Georgiy A
GA
Kaplanskaya
Irina B
IB
Möller
Peter
P
Parwaresch
Reza M
RM
Rüdiger
Thomas
T
Stein
Harald
H
Küppers
Ralf
R
Hansmann
Martin L
ML
Siebert
Reiner
R
D000293:Adolescent; D000328:Adult; D000368:Aged; D020169:Caspases / Q000235:genetics; D019457:Chromosome Breakage; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D050438:Genes, Immunoglobulin Heavy Chain; D016259:Genes, myc; D006689:Hodgkin Disease / Q000235:genetics*; D006801:Humans; D017578:Immunoglobulin Class Switching; D007127:Immunoglobulin Constant Regions / Q000235:genetics; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; D009363:Neoplasm Proteins / Q000235:genetics; D051560:Proto-Oncogene Proteins c-bcl-6; D012008:Recurrence; D016539:Reed-Sternberg Cells / Q000378:metabolism*; D014178:Translocation, Genetic
C084103:BCL6 protein, human; D004268:DNA-Binding Proteins; D007127:Immunoglobulin Constant Regions; D009363:Neoplasm Proteins; D051560:Proto-Oncogene Proteins c-bcl-6; D020169:Caspases; C400109:MALT1 protein, human; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein