title: A comprehensive analysis of the cellular and EBV-specific microRNAome in primary CNS PTLD identifies different patterns among EBV-associated tumors.
abstract: Primary central nervous system (pCNS) posttransplant lymphoproliferative disorder (PTLD) is a complication of solid organ transplantation characterized by poor outcome. In contrast to systemic PTLD, Epstein-Barr virus (EBV)-association of pCNS PTLD is almost universal, yet viral and cellular data are limited. To identify differences in the pattern of EBV-association of pCNS and systemic PTLD, we analyzed the expression of latent and lytic EBV transcripts and the viral and cellular microRNAome in nine pCNS (eight EBV-associated) and in 16 systemic PTLD samples (eight EBV-associated). Notably although 15/16 EBV-associated samples exhibited a viral type III latency pattern, lytic transcripts were also strongly expressed. Members of the ebv-miR-BHRF1 and ebv-miR-BART clusters were expressed in virtually all EBV-associated PTLD samples. There were 28 cellular microRNAs differentially expressed between systemic and pCNS PTLD. pCNS PTLD expressed lower hsa-miR-199a-5p/3p and hsa-miR-143/145 (implicated in nuclear factor kappa beta and c-myc signaling) as compared to systemic PTLD. Unsupervised nonhierarchical clustering of the viral and cellular microRNAome distinguished non-EBV-associated from EBV-associated samples and identified a separate group of EBV-associated pCNS PTLD that displayed reduced levels of B cell lymphoma associated oncomiRs such as hsa-miR-155, -21, -221 and the hsa-miR-17-92 cluster. EBV has a major impact on viral and cellular microRNA expression in EBV-associated pCNS PTLD.
authors.affiliation: Clinical Immunohaematology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Australia; Department of Hematology and Oncology, Charité - Universitätsmedizin Berlin, Campus Virchow Clinic, Berlin, Germany.
authors.forename: S E K
authors.initials: SE
authors.lastname: Fink
authors.forename: M K
authors.initials: MK
authors.lastname: Gandhi
authors.forename: J P
authors.initials: JP
authors.lastname: Nourse
authors.forename: C
authors.initials: C
authors.lastname: Keane
authors.forename: K
authors.initials: K
authors.lastname: Jones
authors.forename: P
authors.initials: P
authors.lastname: Crooks
authors.forename: K
authors.initials: K
authors.lastname: Jöhrens
authors.forename: A
authors.initials: A
authors.lastname: Korfel
authors.forename: H
authors.initials: H
authors.lastname: Schmidt
authors.forename: S
authors.initials: S
authors.lastname: Neumann
authors.forename: A
authors.initials: A
authors.lastname: Tiede
authors.forename: U
authors.initials: U
authors.lastname: Jäger
authors.forename: U
authors.initials: U
authors.lastname: Dührsen
authors.forename: R
authors.initials: R
authors.lastname: Neuhaus
authors.forename: M
authors.initials: M
authors.lastname: Dreyling
authors.forename: K
authors.initials: K
authors.lastname: Borchert
authors.forename: T
authors.initials: T
authors.lastname: Südhoff
authors.forename: H
authors.initials: H
authors.lastname: Riess
authors.forename: I
authors.initials: I
authors.lastname: Anagnostopoulos
authors.forename: R U
authors.initials: RU
authors.lastname: Trappe
mesh_terms: D002461:Cell Line, Transformed; D016543:Central Nervous System Neoplasms / Q000235:genetics* / Q000821:virology; D005260:Female; D020869:Gene Expression Profiling; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D008232:Lymphoproliferative Disorders / Q000235:genetics* / Q000821:virology; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D059467:Transcriptome
chemical_list: D035683:MicroRNAs
keywords: Kidney transplantation/nephrology; molecular biology: micro RNA; posttransplant lymphoproliferative disorder (PTLD); translational research/science