Splenic marginal zone lymphoma: comprehensive analysis of gene expression and miRNA profiling

Abstract

Splenic marginal zone lymphoma is a small B-cell neoplasm whose molecular pathogenesis is still essentially unknown and whose differentiation from other small B-cell lymphomas is hampered by the lack of specific markers. We have analyzed the gene expression and miRNA profiles of 31 splenic marginal zone lymphoma cases. For comparison, 7 spleens with reactive lymphoid hyperplasia, 10 spleens infiltrated by chronic lymphocytic leukemia, 12 spleens with follicular lymphoma, 6 spleens infiltrated by mantle cell lymphoma and 15 lymph nodes infiltrated by nodal marginal zone lymphoma were included. The results were validated by qRT-PCR in an independent series including 77 paraffin-embedded splenic marginal zone lymphomas. The splenic marginal zone lymphoma miRNA signature had deregulated expression of 51 miRNAs. The most highly overexpressed miRNAs were miR-155, miR-21, miR-34a, miR-193b and miR-100, while the most repressed miRNAs were miR-377, miR-27b, miR-145, miR-376a and miR-424. MiRNAs located in 14q32-31 were underexpressed in splenic marginal zone lymphoma compared with reactive lymphoid tissues and other B-cell lymphomas. Finally, the gene expression data were integrated with the miRNA profile to identify functional relationships between genes and deregulated miRNAs. Our study reveals miRNAs that are deregulated in splenic marginal zone lymphoma and identifies new candidate diagnostic molecules for splenic marginal zone lymphoma.

DNA methylation profiling identifies two splenic marginal zone lymphoma subgroups with different clinical and genetic features

“…The current work represents the largest study of genome-wide DNA promoter methylation profiling in SMZL and represents a further step in the understanding of this lymphoma subtype after having reported its gene expression and miRNA profiles 30 and its genome-wide DNA profiling, 2 and having characterized the most recurrent somatic mutations in this entity. 4,7,31,32 Disruption of DNA-promoter methylation is an important pathogenetic mechanism in lymphomas and can affect clinical outcome.…”

Whole-exome sequencing in splenic marginal zone lymphoma reveals mutations in genes involved in marginal zone differentiation

“…3,4 The results of gene expression profiling have revealed a molecular signature of SMZL based on nuclear factor kB (NF-kB) activation and increased signalling from B-cell receptor (BCR) and tumour necrosis factor, together with other genes such as AKT, AP1, NOTCH2 and TCL1. 5 A next-generation sequencing strategy has recently been used to explore the genome and exome of a series of SMZL patients, revealing recurrent mutations in NOTCH2 and in genes implicated in BCR and NF-kB signalling. 6,7 Using whole-exome sequencing (WES) of a series of SMZL samples, we have identified mutations in genes involved in pathways that are key players in marginal zone differentiation and other essential functions of the cell.…”

NF-κB directly mediates epigenetic deregulation of common microRNAs in Epstein-Barr virus-mediated transformation of B-cells and in lymphomas

“…It has also been demonstrated that miR-155 is upregulated following EBV infection. These miRNAs are also strongly upregulated in B cell lymphomas (11,12) and it has been proposed that miRNAs misregulation in lymphomas could be used for diagnosis, prognosis or prediction of response to specific therapies (13). As aforementioned, DLBCL is one of the B cell lymphoma types associated with EBV (14) and also the most common type of lymphoma, accounting for 30–40% of lymphomas in western countries.…”