title: Prevalence of targetable oncogenic mutations and genomic alterations in Epstein-Barr virus-associated diffuse large B-cell lymphoma of the elderly.
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.
authors.affiliation: Department of Internal Medicine I, University Hospital of Schleswig-Holstein , Luebeck , Germany.
authors.forename: Niklas
authors.initials: N
authors.lastname: Gebauer
authors.forename: Judith
authors.initials: J
authors.lastname: Gebauer
authors.forename: Tim Tristan
authors.initials: TT
authors.lastname: Hardel
authors.forename: Veronica
authors.initials: V
authors.lastname: Bernard
authors.forename: Harald
authors.initials: H
authors.lastname: Biersack
authors.forename: Hendrik
authors.initials: H
authors.lastname: Lehnert
authors.forename: Dirk
authors.initials: D
authors.lastname: Rades
authors.forename: Alfred Christian
authors.initials: AC
authors.lastname: Feller
authors.forename: Christoph
authors.initials: C
authors.lastname: Thorns
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D053468:CARD Signaling Adaptor Proteins / Q000235:genetics / Q000378:metabolism; D051925:CD79 Antigens / Q000235:genetics / Q000378:metabolism; D002869:Chromosome Aberrations; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D020031:Epstein-Barr Virus Infections / Q000150:complications*; D005260:Female; D006162:Guanylate Cyclase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D016403:Lymphoma, Large B-Cell, Diffuse / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism; D015513:Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D015995:Prevalence; D046888:Tissue Array Analysis
chemical_list: D053468:CARD Signaling Adaptor Proteins; D051925:CD79 Antigens; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D015513:Oncogene Proteins; C426242:CARD11 protein, human; D006162:Guanylate Cyclase
keywords: Epstein–Barr virus-associated diffuse large B-cell lymphoma of the elderly; NF-κB pathway; array comparative genomic hybridization; chromatin remodeling