title: Gene expression profiling reveals clear differences between EBV-positive and EBV-negative posttransplant lymphoproliferative disorders.
abstract: Posttransplant patients are at risk of developing a potentially life-threatening posttransplantation lymphoproliferative disorder (PTLD), most often of diffuse large B cell lymphoma (DLBCL) morphology and associated with Epstein-Barr Virus (EBV) infection. The aim of this study was to characterize the clinicopathological and molecular-genetic characteristics of posttransplant DLBCL and to elucidate whether EBV(+) and EBV(-) posttransplant DLBCL are biologically different. We performed gene expression profiling studies on 48 DLBCL of which 33 arose posttransplantation (PT-DLBCL; 72% EBV+) and 15 in immunocompetent hosts (IC-DLBCL; none EBV+). Unsupervised hierarchical analysis showed clustering of samples related to EBV-status rather than immune status. Except for decreased T cell signaling these cases were inseparable from EBV(-) IC-DLBCL. In contrast, a viral response signature clearly segregated EBV(+) PT-DLBCL from EBV(-) PT-DLBCL and IC-DLBCL cases that were intermixed. The broad EBV latency profile (LMP1+/EBNA2+) was expressed in 59% of EBV(+) PT-DLBCL and associated with a more elaborate inflammatory response compared to intermediate latency (LMP1+/EBNA2-). Inference analysis revealed a role for innate and tolerogenic immune responses (including VSIG4 and IDO1) in EBV(+) PT-DLBCL. In conclusion we can state that the EBV signature is the most determining factor in the pathogenesis of EBV(+) PT-DLBCL.
authors.affiliation: Translational Cell and Tissue Research, KU Leuven, Leuven, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Morscio
authors.forename: D
authors.initials: D
authors.lastname: Dierickx
authors.forename: J F
authors.initials: JF
authors.lastname: Ferreiro
authors.forename: A
authors.initials: A
authors.lastname: Herreman
authors.forename: P
authors.initials: P
authors.lastname: Van Loo
authors.forename: E
authors.initials: E
authors.lastname: Bittoun
authors.forename: G
authors.initials: G
authors.lastname: Verhoef
authors.forename: P
authors.initials: P
authors.lastname: Matthys
authors.forename: J
authors.initials: J
authors.lastname: Cools
authors.forename: I
authors.initials: I
authors.lastname: Wlodarska
authors.forename: C
authors.initials: C
authors.lastname: De Wolf-Peeters
authors.forename: X
authors.initials: X
authors.lastname: Sagaert
authors.forename: T
authors.initials: T
authors.lastname: Tousseyn
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002675:Child, Preschool; D020031:Epstein-Barr Virus Infections / Q000150:complications* / Q000235:genetics / Q000821:virology; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D017403:In Situ Hybridization; D008232:Lymphoproliferative Disorders / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016377:Organ Transplantation; D012189:Retrospective Studies; D014764:Viral Proteins / Q000096:biosynthesis* / Q000235:genetics; D017735:Virus Latency; D055815:Young Adult
chemical_list: D014764:Viral Proteins