Oncotarget

Research Papers: Pathology:

MicroRNAs sequencing unveils distinct molecular subgroups of plasmablastic lymphoma

Maria Raffaella Ambrosio, Lucia Mundo, Sara Gazaneo, Matteo Picciolini, Prasad Satya Vara, Shaheen Sayed, Alessandro Ginori, Giuseppe Lo Bello, Leonardo Del Porro, Mohsen Navari, Stefano Ascani, Amhed Yonis, Lorenzo Leoncini _, Pier Paolo Piccaluga and Stefano Lazzi

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Oncotarget. 2017; 8:107356-107373. https://doi.org/10.18632/oncotarget.22219

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Abstract

Maria Raffaella Ambrosio1,*, Lucia Mundo1,*, Sara Gazaneo1, Matteo Picciolini2, Prasad Satya Vara3, Shaheen Sayed4, Alessandro Ginori1,5, Giuseppe Lo Bello1, Leonardo Del Porro1, Mohsen Navari6,7,8, Stefano Ascani9, Amhed Yonis10, Lorenzo Leoncini1, Pier Paolo Piccaluga7,8,* and Stefano Lazzi1,*

1 Department of Medical Biotechnology, Section of Pathology, University of Siena, Siena, Italy

2 Diatech Pharmacogenetics, Jesi, Italy

3 Aga Khan Hospital, Kisumu, Kenya

4 Aga Khan University Hospital, Nairobi, Kenya

5 Pathology Unit, Ospedale Civico di Carrara, Carrara, Italy

6 Research Center of Advanced Technologies in Medicine, Torbat Heydariyeh University of Medical Sciences, Torbat Heydariyeh, Iran

7 Department of Experimental, Diagnostic, and Experimental Medicine, Bologna University School of Medicine, Bologna, Italy

8 Euro-Mediterranean Institute of Science and Technology (IEMEST), Palermo, Italy

9 Section of Pathology, Azienda Ospedaliera S. Maria di Terni, University of Perugia, Perugia, Italy

10 Alexandria University, Alexandria, Egypt

* These authors have contributed equally to this work

Correspondence to:

Lorenzo Leoncini, email:

Pier Paolo Piccaluga, email:

Keywords: plasmablastic lymphoma; miRNA expression profiling; Burkitt lymphoma; extramedullary plasmacytoma; Epstein-Barr virus; Pathology section

Received: June 20, 2017 Accepted: September 08, 2017 Published: October 31, 2017

Abstract

Plasmablastic lymphoma (PBL) is an aggressive lymphoma, often arising in the context of immunodeficiency and associated with Epstein-Barr virus (EBV) infection. The most frequently detected genetic alteration is the deregulation of MYC gene through the translocation - t(8;14)(q24;q32). The diagnosis of PBL is often challenging because it has an overlap in morphology, immunophenotype, cytogenetics and virus association with other lymphomas and plasma cell neoplasms; further, its molecular basis remains elusive. In the present study we aimed to better define the possible contribution of EBV infection as well as miRNA deregulation in PBL pathogenesis.

We studied 23 cases of PBL, 19 Burkitt lymphomas (BL), and 17 extra-medullary plasmacytoma (EMPC). We used qPCR and immunohistochemistry to assess EBV latency patterns, while micro-RNA (miRNA) profiling was performed by next generation sequencing (Illumina) and validated by qPCR.

Our analysis revealed a non-canonical EBV latency program with the partial expression of some proteins characterizing latency II and the activation of an abortive lytic cycle. Moreover, we identified miRNA signatures discriminating PBL from BL and EMPC. Interestingly, based on the miRNA profile, PBL appeared constituted by two discrete subgroups more similar to either BL or EMPC, respectively. This pattern was confirmed in an independent set of cases studied by qPCR and corresponded to different clinico-pathological features in the two groups, including HIV infection, MYC rearrangement and disease localization.

In conclusion, we uncovered for the first time 1) an atypical EBV latency program in PBL; 2) a miRNA signature distinguishing PBL from the closest malignant counterparts; 3) the molecular basis of PBL heterogeneity.


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