Virus-encoded microRNA contributes to the molecular profile of EBV-positive Burkitt lymphomas.
Burkitt lymphoma (BL) is an aggressive neoplasm characterized by consistent morphology and phenotype, typical clinical behavior and distinctive molecular profile. The latter is mostly driven by the MYC over-expression associated with the characteristic translocation (8;14) (q24; q32) or with variant lesions. Additional genetic events can contribute to Burkitt Lymphoma pathobiology and retain clinical significance. A pathogenetic role for Epstein-Barr virus infection in Burkitt lymphomagenesis has been suggested; however, the exact function of the virus is largely unknown.In this study, we investigated the molecular profiles (genes and microRNAs) of Epstein-Barr virus-positive and -negative BL, to identify specific patterns relying on the differential expression and role of Epstein-Barr virus-encoded microRNAs.First, we found significant differences in the expression of viral microRNAs and in selected target genes. Among others, we identified LIN28B, CGNL1, GCET2, MRAS, PLCD4, SEL1L, SXX1, and the tyrosine kinases encoding STK10/STK33, all provided with potential pathogenetic significance. GCET2, also validated by immunohistochemistry, appeared to be a useful marker for distinguishing EBV-positive and EBV-negative cases. Further, we provided solid evidences that the EBV-encoded microRNAs (e.g. BART6) significantly mold the transcriptional landscape of Burkitt Lymphoma clones.In conclusion, our data indicated significant differences in the transcriptional profiles of EBV-positive and EBV-negative BL and highlight the role of virus encoded miRNA.
Hematopathology Section, Department of Experimental, Diagnostic, and Experimental Medicine, S. Orsola-Malpighi Hospital, Bologna University School of Medicine, Bologna, Italy.
Pier Paolo
PP
Piccaluga
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.
Mohsen
M
Navari
Department of Medical Biotechnology, University of Siena, Siena, Italy.|School of Biological and Chemical Sciences, Queen Mary University of London, London, UK.
Giulia
G
De Falco
Department of Medical Biotechnology, University of Siena, Siena, Italy.
Maria Raffaella
MR
Ambrosio
Department of Medical Biotechnology, University of Siena, Siena, Italy.
Stefano
S
Lazzi
Hematopathology Section, Department of Experimental, Diagnostic, and Experimental Medicine, S. Orsola-Malpighi Hospital, Bologna University School of Medicine, Bologna, Italy.
Fabio
F
Fuligni
Department of Medical Biotechnology, University of Siena, Siena, Italy.
Cristiana
C
Bellan
Hematopathology Section, Department of Experimental, Diagnostic, and Experimental Medicine, S. Orsola-Malpighi Hospital, Bologna University School of Medicine, Bologna, Italy.
Maura
M
Rossi
Hematopathology Section, Department of Experimental, Diagnostic, and Experimental Medicine, S. Orsola-Malpighi Hospital, Bologna University School of Medicine, Bologna, Italy.
Maria Rosaria
MR
Sapienza
Hematopathology Section, Department of Experimental, Diagnostic, and Experimental Medicine, S. Orsola-Malpighi Hospital, Bologna University School of Medicine, Bologna, Italy.
Maria Antonella
MA
Laginestra
Hematopathology Section, Department of Experimental, Diagnostic, and Experimental Medicine, S. Orsola-Malpighi Hospital, Bologna University School of Medicine, Bologna, Italy.
Maryam
M
Etebari
Department of Pathology, University of Nairobi, Nairobi, Kenya.
Emily A
EA
Rogena
Department of Pathology, Makerere University, Kampala, Uganda.
Lynnette
L
Tumwine
Tumour Immunology Unit, Department of Health Science, Human Pathology Section, Palermo University School of Medicine, Palermo, Italy.
Claudio
C
Tripodo
Department of Pathology and Diagnostic, University of Verona, Verona, Italy.
Davide
D
Gibellini
Department of Molecular Virology, Immunology, and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
Jessica
J
Consiglio
Department of Molecular Virology, Immunology, and Medical Genetics, Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
Carlo M
CM
Croce
Diagnostic Hematopathology Unit, European Institute of Oncology, Milan, Italy.
Stefano A
SA
Pileri
Department of Medical Biotechnology, University of Siena, Siena, Italy.
Lorenzo
L
Leoncini
D002051:Burkitt Lymphoma / Q000235:genetics* / Q000821:virology; D016000:Cluster Analysis; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D020031:Epstein-Barr Virus Infections / Q000235:genetics* / Q000821:virology; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000502:physiology; D054884:Host-Pathogen Interactions / Q000235:genetics; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D035683:MicroRNAs / Q000235:genetics*; D008840:Microfilament Proteins; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D054803:Phospholipase C delta / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
C533277:CGNL1 protein, human; D003598:Cytoskeletal Proteins; C476824:GCSAM protein, human; D047908:Intracellular Signaling Peptides and Proteins; C516326:LIN28B protein, human; C109523:MRAS protein, human; D035683:MicroRNAs; D008840:Microfilament Proteins; D009363:Neoplasm Proteins; D012367:RNA, Viral; D016601:RNA-Binding Proteins; C518030:PLCD4 protein, human; D054803:Phospholipase C delta; D018631:ras Proteins
BART6; Burkitt lymphoma; EBV; miRNA; pathogenesis