title: Differential micro-RNA expression in primary CNS and nodal diffuse large B-cell lymphomas.
abstract: Most primary CNS lymphomas (PCNSL) are diffuse large B-cell lymphomas (DLBCL). However, clinical behavior and prognosis differ considerably from those for nodal DLBCL (nDLBCL), and their pathogenesis is still not fully understood. Micro-RNAs (miRNAs) have been associated with cancer development and progression. We investigated a large miRNA panel for differential expression in PCNSL and nDLBCL, to determine new mechanisms potentially involved in PCNSL pathogenesis. Using paraffin-embedded biopsy specimens from 21 HIV-negative patients with newly diagnosed PCNSL (n = 11) and nDLBCL (n= 10), we measured the expression of 365 miRNA species by quantitative real-time PCR using low-density PCR arrays. We found that 18 miRNAs were differentially expressed: median expression levels of 13 miRNAs were 2.1-13.1 times higher in PCNSL, and median expression levels of 5 miRNAs were 2.6-3.3 times higher in nDLBCL. MiRNAs upregulated in PCNSL were associated with the Myc pathway (miR-17-5p, miR-20a, miR-9), with blocking of terminal B-cell differentiation (miR-9, miR-30b/c), or with upregulation by inflammatory cytokines (miR-155). Putative tumor-suppressor miRNAs (miR-199a, miR-214, miR-193b, miR-145) were downregulated in PCNSL. There was no overlap of miRNAs dysregulated in PCNSL with those differentially expressed between immunohistologically defined germinal center B cell-like (GCB) and non-GCB types or, apart from miR-9, with miRNAs known to be overexpressed in human brain. We conclude that PCNSL exhibits a distinct pattern of miRNA expression compared with nDLBCL. This argues for the involvement of different molecular mechanisms in the pathogenesis of these two lymphoma types.
authors.affiliation: Department of Hematology and Oncology, Charité Universitätsmedizin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany. lars.fischer@charite.de
authors.forename: Lars
authors.initials: L
authors.lastname: Fischer
authors.forename: Michael
authors.initials: M
authors.lastname: Hummel
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Korfel
authors.forename: Dido
authors.initials: D
authors.lastname: Lenze
authors.forename: Korrina
authors.initials: K
authors.lastname: Joehrens
authors.forename: Eckhard
authors.initials: E
authors.lastname: Thiel
mesh_terms: D000368:Aged; D016543:Central Nervous System Neoplasms / Q000235:genetics* / Q000473:pathology; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000473:pathology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000032:analysis*; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D035683:MicroRNAs