Prevalence of targetable oncogenic mutations and genomic alterations in Epstein-Barr virus-associated diffuse large B-cell lymphoma of the elderly

• Published in: Leukemia & lymphoma 2015-04, Vol.56 (4), p.1100-1106
• Main Authors: Gebauer, Niklas, Gebauer, Judith, Hardel, Tim Tristan, Bernard, Veronica, Biersack, Harald, Lehnert, Hendrik, Rades, Dirk, Feller, Alfred Christian, Thorns, Christoph
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; array comparative genomic hybridization; CARD Signaling Adaptor Proteins - genetics; CARD Signaling Adaptor Proteins - metabolism; CD79 Antigens - genetics; CD79 Antigens - metabolism; chromatin remodeling; Chromosome Aberrations; Comparative Genomic Hybridization; DNA Copy Number Variations; Epstein-Barr Virus Infections - complications; Epstein-Barr virus-associated diffuse large B-cell lymphoma of the elderly; Female; Guanylate Cyclase - genetics; Guanylate Cyclase - metabolism; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Lymphoma, Large B-Cell, Diffuse - complications; Lymphoma, Large B-Cell, Diffuse - epidemiology; Lymphoma, Large B-Cell, Diffuse - genetics; Male; Middle Aged; Mutation; Myeloid Differentiation Factor 88 - genetics; Myeloid Differentiation Factor 88 - metabolism; NF-κB pathway; Oncogene Proteins - genetics; Oncogene Proteins - metabolism; Prevalence; Tissue Array Analysis
• ISSN: 1042-8194; 1029-2403
• DOI: 10.3109/10428194.2014.944522

Abstract Epstein-Barr virus (EBV)-associated diffuse large B-cell lymphoma (DLBCL) of the elderly constitutes a provisional clinicopathological entity in the current World Health Organization (WHO) classification and its genomic features remain sparsely characterized. We investigated a cohort of 26 cases of untreated de novo EBV-positive DLBCL of the elderly by high-resolution array-based comparative genomic profiling and fluorescence in situ hybridization (FISH). Moreover, we screened for activating mutations affecting nuclear factor (NF)-κB pathway signaling and chromatin remodeling (EZH2, CD79B, CARD11 and MYD88) due to their impact of gene expression signatures and postulated upcoming therapeutic targetability. We identified an overlap between genomic aberrations previously described to be exclusive features of plasmablastic lymphoma (PL), post-transplant lymphoproliferative disorder (PTLD) and DLBCL, respectively, indicating a close cytogenetic relationship between these entities. Few mutations affecting CD79B and CARD11 and no MYD88 mutations were detectable, hinting at EBV-mediated activation of NF-κB as an alternative to pathologically enforced B-cell receptor signaling in this rare entity.