title: Novel IGH and MYC Translocation Partners in Diffuse Large B-Cell Lymphomas.
abstract: Chromosomal translocations involving an immunoglobulin (IG) locus and a proto-oncogene play a major role in diffuse large B-cell lymphoma (DLBCL) pathogenesis. Recurrent IG translocation partners in DLBCL are the BCL6, BCL2, and MYC genes, but other rare translocation partners are also known. We studied 20 DLBCL with fluorescence in situ hybridization-based evidence for IG heavy chain (IGH) locus-associated translocations not involving BCL6, BCL2, MALT1, or MYC by long distance inverse PCR to identify the translocation partners. Moreover, we studied eight DLBCL with MYC translocations not involving IG or known non-IG loci as translocation partner to search for novel MYC translocations. We identified three novel IGH-associated translocations. Chromosomal breakpoints involved the IMMP2L gene in 7q31, the BCAS2 gene in 1p13, and the PVRL2 gene in 19q13. The latter gene, which is recurrently translocated in T-cell lymphomas, is significantly higher expressed in the biopsy with the translocation compared to cases without this genetic aberration, indicating a pathogenetic role of PVRL2 also in DLBCL. In one case with a MYC break we obtained a novel MYC-SOCS1 translocation representing an unusual translocation of a proto-oncogene with a tumor suppressor gene. Indeed, we demonstrate that the oncogene was deregulated and the tumor suppressor gene inactivated. As both genes undergo aberrant somatic hypermutation in the region of the chromosomal breakpoints, this translocation likely happened as a byproduct of the hypermutation process. Overall, our study suggests that chromosomal translocations in DLBCL are more heterogeneous than previously known. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Institute of Cell Biology (Cancer Research), University of Duisburg-Essen, Medical School, Essen, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Otto
authors.affiliation: Institute of Cell Biology (Cancer Research), University of Duisburg-Essen, Medical School, Essen, Germany.
authors.forename: René
authors.initials: R
authors.lastname: Scholtysik
authors.affiliation: Institute of Cell Biology (Cancer Research), University of Duisburg-Essen, Medical School, Essen, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Schmitz
authors.affiliation: Institute for Medical Informatics, Statistics and Epidemiology (IMISE), University of Leipzig, Leipzig, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Kreuz
authors.affiliation: Institute of Human Genetics, Christian-Albrechts University Kiel & University Hospital Schleswig-Holstein, Kiel, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Becher
authors.affiliation: Institute of Pathology, Berlin, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Hummel
authors.affiliation: Institute of Pathology, University of Würzburg, Würzburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Rosenwald
authors.affiliation: Department of Hematology/Oncology, University Hospital Göttingen, Göttingen, Germany.
authors.forename: Lorenz
authors.initials: L
authors.lastname: Trümper
authors.affiliation: Department of Pathology, Hematopathology Section and Lymph Node Registry, University Hospital Schleswig-Holstein, Campus Kiel/Christian-Albrechts-University, Kiel, Germany.
authors.forename: Wolfram
authors.initials: W
authors.lastname: Klapper
authors.affiliation: Institute of Human Genetics, Christian-Albrechts University Kiel & University Hospital Schleswig-Holstein, Kiel, Germany.|Institute of Human Genetics, University of Ulm, Ulm, Germany.
authors.forename: Reiner
authors.initials: R
authors.lastname: Siebert
authors.affiliation: Institute of Cell Biology (Cancer Research), University of Duisburg-Essen, Medical School, Essen, Germany. ralf.kueppers@uk-essen.de.
authors.forename: Ralf
authors.initials: R
authors.lastname: Küppers
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D015815:Cell Adhesion Molecules / Q000235:genetics; D002648:Child; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D010450:Endopeptidases / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D000075983:Nectins; D009363:Neoplasm Proteins / Q000235:genetics; D009367:Neoplasm Staging; D011379:Prognosis; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D014178:Translocation, Genetic / Q000235:genetics*
chemical_list: C120624:BCAS2 protein, human; D014408:Biomarkers, Tumor; D015815:Cell Adhesion Molecules; D007143:Immunoglobulin Heavy Chains; C000715470:MAS1 protein, human; C489427:MYC protein, human; D000075983:Nectins; D009363:Neoplasm Proteins; D000090063:Proto-Oncogene Mas; D016271:Proto-Oncogene Proteins c-myc; D010450:Endopeptidases; C425070:IMMP2L protein, human