title: Chromosomal breakpoints affecting immunoglobulin loci are recurrent in Hodgkin and Reed-Sternberg cells of classical Hodgkin lymphoma.
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.
authors.affiliation: Institutes of Human Genetics and Hematopathology, University Hospital Schleswig-Holstein Campus Kiel, Kiel, Germany.
authors.forename: José I
authors.initials: JI
authors.lastname: Martín-Subero
authors.forename: Wolfram
authors.initials: W
authors.lastname: Klapper
authors.forename: Anna
authors.initials: A
authors.lastname: Sotnikova
authors.forename: Evelyne
authors.initials: E
authors.lastname: Callet-Bauchu
authors.forename: Lana
authors.initials: L
authors.lastname: Harder
authors.forename: Christian
authors.initials: C
authors.lastname: Bastard
authors.forename: Roland
authors.initials: R
authors.lastname: Schmitz
authors.forename: Susanne
authors.initials: S
authors.lastname: Grohmann
authors.forename: Jorge
authors.initials: J
authors.lastname: Höppner
authors.forename: Jennifer
authors.initials: J
authors.lastname: Riemke
authors.forename: Thomas F E
authors.initials: TF
authors.lastname: Barth
authors.forename: Françoise
authors.initials: F
authors.lastname: Berger
authors.forename: Heinz-Wolfram
authors.initials: HW
authors.lastname: Bernd
authors.forename: Alexander
authors.initials: A
authors.lastname: Claviez
authors.forename: Stefan
authors.initials: S
authors.lastname: Gesk
authors.forename: Georgiy A
authors.initials: GA
authors.lastname: Frank
authors.forename: Irina B
authors.initials: IB
authors.lastname: Kaplanskaya
authors.forename: Peter
authors.initials: P
authors.lastname: Möller
authors.forename: Reza M
authors.initials: RM
authors.lastname: Parwaresch
authors.forename: Thomas
authors.initials: T
authors.lastname: Rüdiger
authors.forename: Harald
authors.initials: H
authors.lastname: Stein
authors.forename: Ralf
authors.initials: R
authors.lastname: Küppers
authors.forename: Martin L
authors.initials: ML
authors.lastname: Hansmann
authors.forename: Reiner
authors.initials: R
authors.lastname: Siebert
mesh_terms: 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
chemical_list: 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