Diffuse Large B-cell Lymphomas of Immunoblastic Type Are a Major Reservoir for MYC-IGH Translocations. (January 2015)

• Record Type: Journal Article
• Authors: Horn, Heike; Staiger, Annette M.; Vöhringer, Matthias; Hay, Ulrich; Campo, Elias; Rosenwald, Andreas; Ott, German; Ott, M. Michaela
• Is Part Of: American journal of surgical pathology. Volume 39:Number 1(2015)
• Publication Date: 2015-01
• Subjects: Pathology, Surgical -- Periodicals; 617.0705
• DOI: 10.1097/PAS.0000000000000319
• Languages: English
• ISSNs: 0147-5185

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <p>The immunoblastic variant of diffuse large B-cell lymphoma (IB-DLBCL) has recently been recognized as an aggressive lymphoma type with inferior prognosis as compared with other DLBCL variants. At the same time, the presence of <italic>MYC</italic> rearrangements in DLBCL has been shown to indicate shorter survival in R-CHOP-treated patients. In this study, we investigated the occurrence of <italic>MYC</italic> gene rearrangements in IB-DLBCL versus non-IB-DLBCL in a large series. Using fluorescence in situ hybridization with an <italic>MYC</italic> break-apart and <italic>MYC</italic>-<italic>IGH</italic> fusion probe, we found that 13/39 evaluable IB-DLBCLs (33%) harbor translocations involving <italic>MYC</italic>, in contrast with only 5/68 (7%) in the non-IB-DLBCL group (<italic>P</italic><0.01). The immunoglobulin heavy chain gene (<italic>IGH</italic>) was the translocation partner in all rearrangements (100%) involving <italic>MYC</italic> in IB-DLBCL, which is in contrast to what has been reported for DLBCL in the literature (50% to 70%). Moreover, <italic>MYC</italic> rearrangements occurred as the sole translocation in the majority of cases (77%), whereas across all DLBCLs the majority of <italic>MYC</italic>-rearranged cases carry additional rearrangements of either <italic>BCL2</italic> and/or <italic>BCL6</italic> genes (between 58% and 83% of cases). Finally, <italic>MYC</italic>-rearranged IB-DLBCLs were CD10 positive in 62% (8/13), whereas this was an uncommon feature in <italic>MYC</italic> germline IB-DLBCLs (15%). In conclusion, IB-DLBCLs are genetically characterized by frequent <italic>MYC</italic>-<italic>IGH</italic> translocations that often occur without additional <italic>BCL2</italic> and/or <italic>BCL6</italic> translocations. The activation of <italic>MYC</italic>, therefore, may be an important pathogenetic feature in IB-DLBCL.</p> </sec> </abstract>