title: Molecular signature of Epstein Barr virus-positive Burkitt lymphoma and post-transplant lymphoproliferative disorder suggest different roles for Epstein Barr virus.
abstract: Epstein Barr virus (EBV) infection is commonly associated with human cancer and, in particular, with lymphoid malignancies. Although the precise role of the virus in the pathogenesis of different lymphomas is largely unknown, it is well recognized that the expression of viral latent proteins and miRNA can contribute to its pathogenetic role. In this study, we compared the gene and miRNA expression profile of two EBV-associated aggressive B non-Hodgkin lymphomas known to be characterized by differential expression of the viral latent proteins aiming to dissect the possible different contribution of such proteins and EBV-encoded miRNAs. By applying extensive bioinformatic inferring and an experimental model, we found that EBV+ Burkitt lymphoma presented with significant over-expression of EBV-encoded miRNAs that were likely to contribute to its global molecular profile. On the other hand, EBV+ post-transplant diffuse large B-cell lymphomas presented a significant enrichment in genes regulated by the viral latent proteins. Based on these different viral and cellular gene expression patterns, a clear distinction between EBV+ Burkitt lymphoma and post-transplant diffuse large B-cell lymphomas was made. In this regard, the different viral and cellular expression patterns seemed to depend on each other, at least partially, and the latency type most probably played a significant role in their regulation. In conclusion, our data indicate that EBV influence over B-cell malignant clones may act through different mechanisms of transcriptional regulation and suggest that potentially different pathogenetic mechanisms may depend upon the conditions of the interaction between EBV and the host that finally determine the latency pattern.
authors.affiliation: Hematopathology Section, Department of Experimental, Diagnostic, and Experimental Medicine, S. Orsola-Malpighi Hospital, Bologna University School of Medicine Bologna, Italy ; Department of Medical Biotechnology, University of Siena Siena, Italy ; Department of Basic sciences, Torbat Heydariyeh University of Medical Sciences Torbat Heydariyeh, Iran.
authors.forename: Mohsen
authors.initials: M
authors.lastname: Navari
authors.affiliation: Hematopathology Section, Department of Experimental, Diagnostic, and Experimental Medicine, S. Orsola-Malpighi Hospital, Bologna University School of Medicine Bologna, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Fuligni
authors.affiliation: Hematopathology Section, Department of Experimental, Diagnostic, and Experimental Medicine, S. Orsola-Malpighi Hospital, Bologna University School of Medicine Bologna, Italy.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Laginestra
authors.affiliation: Hematopathology Section, Department of Experimental, Diagnostic, and Experimental Medicine, S. Orsola-Malpighi Hospital, Bologna University School of Medicine Bologna, Italy.
authors.forename: Maryam
authors.initials: M
authors.lastname: Etebari
authors.affiliation: Department of Medical Biotechnology, University of Siena Siena, Italy.
authors.forename: Maria R
authors.initials: MR
authors.lastname: Ambrosio
authors.affiliation: Hematopathology Section, Department of Experimental, Diagnostic, and Experimental Medicine, S. Orsola-Malpighi Hospital, Bologna University School of Medicine Bologna, Italy.
authors.forename: Maria R
authors.initials: MR
authors.lastname: Sapienza
authors.affiliation: Hematopathology Section, Department of Experimental, Diagnostic, and Experimental Medicine, S. Orsola-Malpighi Hospital, Bologna University School of Medicine Bologna, Italy.
authors.forename: Maura
authors.initials: M
authors.lastname: Rossi
authors.affiliation: Nanchang Joint Programme in Biomedical Sciences, School of Biological and Chemical Sciences, Queen Mary University of London London, UK.
authors.forename: Giulia
authors.initials: G
authors.lastname: De Falco
authors.affiliation: Microbiology and Virology Unit, Department of Pathology and Diagnostic, University of Verona Verona, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Gibellini
authors.affiliation: Tumour Immunology Unit, Human Pathology Section, Department of Health Science, Palermo University School of Medicine Palermo, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Tripodo
authors.affiliation: Hematopathology Section, Department of Experimental, Diagnostic, and Experimental Medicine, S. Orsola-Malpighi Hospital, Bologna University School of Medicine Bologna, Italy.
authors.forename: Stefano A
authors.initials: SA
authors.lastname: Pileri
authors.affiliation: Department of Medical Biotechnology, University of Siena Siena, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Leoncini
authors.affiliation: Hematopathology Section, Department of Experimental, Diagnostic, and Experimental Medicine, S. Orsola-Malpighi Hospital, Bologna University School of Medicine Bologna, Italy.
authors.forename: Pier P
authors.initials: PP
authors.lastname: Piccaluga
keywords: Burkitt lymphoma; Epstein Barr Virus; MicroRNA; gene expression profiling; latency; post-transplant lymphoproliferative disorder