title: IRF8 is associated with germinal center B-cell-like type of diffuse large B-cell lymphoma and exceptionally involved in translocation t(14;16)(q32.33;q24.1).
abstract: Chromosomal translocations involving the immunoglobulin loci represent frequent oncogenic events in B-cell lymphoma development. Although IRF8 (ICSBP-1) protein expression has been demonstrated in germinal center B-cells and related lymphomas in a single report, the IRF8 gene was not described as an immunoglobulin heavy chain (IGH) translocation partner. In a discovery-driven approach we searched for new translocation partners of IGH in diffuse large B-cell lymphoma (DLBCL) by long distance inverse polymerase chain reaction (LDI-PCR) and Sanger sequencing. A t(14;16)(q32.33;q24.1) IGH/IRF8 was detected in a CD5+de novo DLBCL, confirmed by translocation specific PCR and fluorescence in situ hybridization (FISH) analysis. No further IRF8 aberration could be identified either by LDI-PCR in an additional five CD5+DLBCLs or by FISH on 78 formalin-fixed paraffin-embedded biopsies. Subsequent screening for IRF8 by immunohistochemistry revealed IRF8 expression in 18/78 (23%), correlating with a germinal center B-cell-like (GCB) type of DLBCL. This hitherto unknown translocation t(14;16)(q32.33;q24.1) is likely to represent the initiator of a multistep lymphomagenesis in a CD5+de novo DLBCL.
authors.affiliation: Institute of Surgical Pathology, University Hospital Zurich , Zurich , Switzerland.
authors.forename: Marianne
authors.initials: M
authors.lastname: Tinguely
authors.forename: Svenja
authors.initials: S
authors.lastname: Thies
authors.forename: Simona
authors.initials: S
authors.lastname: Frigerio
authors.forename: Tanja
authors.initials: T
authors.lastname: Reineke
authors.forename: Dimitri
authors.initials: D
authors.lastname: Korol
authors.forename: Dieter R
authors.initials: DR
authors.lastname: Zimmermann
mesh_terms: D000368:Aged; D018951:Antigens, CD20 / Q000378:metabolism; D018956:CD5 Antigens / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D002874:Chromosome Mapping; D002883:Chromosomes, Human, Pair 14; D002885:Chromosomes, Human, Pair 16; D005260:Female; D056726:Genetic Association Studies; D018858:Germinal Center / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D050835:Interferon Regulatory Factors / Q000235:genetics* / Q000378:metabolism*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D008954:Models, Biological; D010641:Phenotype; D014178:Translocation, Genetic; D000099185:Interferon Regulatory Factor-8
chemical_list: D018951:Antigens, CD20; D018956:CD5 Antigens; D050835:Interferon Regulatory Factors; D000099185:Interferon Regulatory Factor-8