title: EBV-Positive and EBV-Negative Posttransplant Diffuse Large B Cell Lymphomas Have Distinct Genomic and Transcriptomic Features.
abstract: The molecular pathogenesis of posttransplant diffuse large B cell lymphoma (PT-DLBCL) is largely unknown. We have recently shown that Epstein-Barr virus-positive (EBV(+)) and -negative (EBV(-)) PT-DLBCL have distinct gene expression profiles, and the transcriptomic profile of EBV(-) PT-DLBCL is similar to that of DLBCL in immunocompetent individuals (IC-DLBCL). To validate these observations at the genomic level, we performed array-comparative genome hybridization (aCGH) analysis of 21 EBV(+) PT-DLBCL, 6 EBV(-) PT-DLBCL, and 11 control IC-DLBCL, and subsequently combined genomic and transcriptomic data. The analysis showed that EBV(+) and EBV(-) PT-DLBCL have distinct aCGH profiles and shared only one recurrent imbalance. EBV(-) PT-DLBCL, however, displayed at least 10 aberrations recurrent in IC-DLBCL, among which characteristic gain of 3/3q and 18q, and loss of 6q23/TNFAIP3 as well as 9p21/CDKN2A. The most prevalent aberration in EBV(+) PT-DLBCL was gain/amplification of 9p24.1 targeting PDCD1LG2/PDL2. Our data indicate that the FOXP1 oncogene and the tumor suppressor CDKNA2 implicated in EBV(-) DLBCL, do not play a critical role in the pathogenesis of EBV(+) PT-DLBCL. Altogether, genomic profiling of PT-/IC-DLBCL confirms that EBV(-) and EBV(+) PT-DLBCL are distinct entities, while EBV(-) PT-DLBCL has features in common with IC-DLBCL. These findings support the hypothesis that EBV(-) PT-DLBCL are de novo lymphomas in transplant recipients.
authors.affiliation: Center for Human Genetics, KU Leuven, Leuven, Belgium.
authors.forename: J Finalet
authors.initials: JF
authors.lastname: Ferreiro
authors.affiliation: Translational Cell and Tissue Research KU Leuven, Department of Pathology UZ Leuven, Leuven, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Morscio
authors.affiliation: Department of Hematology, UZ Leuven, Leuven, Belgium.
authors.forename: D
authors.initials: D
authors.lastname: Dierickx
authors.affiliation: Center for Human Genetics, KU Leuven, Leuven, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Vandenberghe
authors.affiliation: Department of Molecular Medicine, UZ Leuven, Leuven, Belgium.
authors.forename: O
authors.initials: O
authors.lastname: Gheysens
authors.affiliation: Department of Hematology, UZ Leuven, Leuven, Belgium.
authors.forename: G
authors.initials: G
authors.lastname: Verhoef
authors.affiliation: Center for Human Genetics, KU Leuven, Leuven, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Zamani
authors.affiliation: Translational Cell and Tissue Research KU Leuven, Department of Pathology UZ Leuven, Leuven, Belgium.
authors.forename: T
authors.initials: T
authors.lastname: Tousseyn
authors.affiliation: Center for Human Genetics, KU Leuven, Leuven, Belgium.
authors.forename: I
authors.initials: I
authors.lastname: Wlodarska
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D055028:Comparative Genomic Hybridization; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000235:genetics* / Q000821:virology; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D023281:Genomics / Q000379:methods*; D006084:Graft Rejection; D006085:Graft Survival; D004854:Herpesvirus 4, Human; D006801:Humans; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000601:surgery / Q000821:virology; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000235:genetics*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger