Plasmablastic lymphoma (PBL) is an aggressive lymphoma characterized by a terminally differentiated B-cell phenotype that usually occurs in immunocompromised or elderly patients. Although the clinical and pathological characteristics of these tumours have been defined the genetic alterations involved in their pathogenesis are not well known. In this study we have investigated the chromosomal alterations of MYC, BCL2, BCL6, MALT1, PAX5, and IGH loci using fluorescence in situ hybridization (FISH) in 42 plasmablastic lymphomas (PBL) and 3 extracavitary primary effusion lymphomas (PEL). MYC rearrangements were identified in 20 of 41 (49%) PBL and the immunoglobulin (IG) genes were the partners in most tumours. MYC rearrangements were more common in EBV-positive (14 of 19, 74%) than EBV-negative (9 of 21, 43%) tumours (p < 0.05). No rearrangements of BCL2, BCL6, MALT1 or PAX5 were detected in any PBL but gains of these loci were observed in 31-41% of the cases examined. Twelve of the 40 PBL in which 3 or more loci could be investigated had multiple simultaneous gains in 3 or more loci. No differences in the survival of the patients according to MYC were observed but the four patients with the longest survival (>50 months) had no or low number of gains (<3). No rearrangements of any of these loci were seen in PEL. In conclusion, PBL are genetically characterized by frequent IG/MYC translocations and gains in multiple chromosomal loci. The oncogenic activation of MYC in these lymphomas may be an important pathogenetic element associated with EBV infection.

IntroductionMature microRNAs (miRNAs) are naturally occurring small noncoding RNAs that act as negative regulators of gene expression through messenger RNA interference. These molecules were described for the first time in 1993 by Ambros and colleagues in Caenorhabditis elegans (Lee et al 1 ), and to date, hundreds of miRNAs have been identified in other species, including viruses. 2,3 miRNAs are encoded by intronic or intergenic DNA regions, primarily as large molecules that can exceed 1 Kb, and are cleaved by an RNase complex into fragments with characteristic stem-loop structures. In the cytoplasm, a RNase called Dicer further cleaves miRNA to generate a duplex molecule of 21 to 25 nucleotides in length. 4 One of the 2 chains is the mature miRNA that binds a protein complex called the RNA-induced silencing complex (RISC). When a miRNA and a messenger RNA exhibit total complementarities, RISC is capable of degrading target messenger RNA, 4 whereas if an incomplete base pairing complementarity takes place, translational silencing of the target occurs. Through these mechanisms, miRNAs decrease translation of human genes. 5,6 miRNAs play an important role in cellular proliferation and differentiation and embryonic development, and they also act as oncogenes or tumor suppressor genes. 7-10 Notably, the majority of miRNAs are found in cancer-associated genomic regions or in chromosome-fragile sites, 11 suggesting an important role for miRNAs in human tumorigenesis. There is also evidence that the influence of miRNAs in oncogenesis might be indirectly driven. For example, the presence of some viruses in a cell may change the host miRNA pattern. 12 Viruses may participate in the origin of some tumors, such as the Epstein-Barr virus (EBV) in Hodgkin lymphoma (HL).HL is a neoplasm characterized by the presence of relatively few tumoral cells (Hodgkin and Reed-Sternberg cells) in a nonneoplastic microenvironment. 13 Hodgkin and Reed-Sternberg cells arise from germinal center B cells. 14 Classic HL (cHL) is subclassified according to the morphology of Reed-Sternberg cells and the composition of the cellular background into nodular sclerosis, mixed cellularity, lymphocyte-rich, and lymphocyte depletion. 15 The 2 former subtypes are the most frequent forms of cHL and contain a variable proportion of neoplastic cells.EBV is present in the malignant cells of 40% to 60% of cHL patients. However, the precise role of the EBV in the pathogenesis of cHL is unknown. It has been reported that viruses have their own miRNA set, 16 and that there is an interaction between the host miRNAs and virus miRNAs. 17,18 The interaction between the virus and the malignant cells in cHL might be mediated in part by miRNAs.To investigate whether a specific expression signature of miRNAs is associated with cHL, we assessed the expression of 156 miRNAs, the majority of which are related to hematopoiesis or tumorigenesis, 7,8,11 in lymph nodes from patients with nodular sclerosis and mixed cellularity cHL and compared the expression patterns with tho...

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