title: A 9 series microRNA signature differentiates between germinal centre and activated B-cell-like diffuse large B-cell lymphoma cell lines.
abstract: The microRNAs are endogenous, non-coding RNAs that play key roles in a range of pathophysiological processes by up- or down-regulating gene expression. Recent studies have shown that some microRNAs have oncogenic or tumour suppressor activity. Diffuse large B-cell lymphoma (DLBCL) is an aggressive non-Hodgkin's lymphoma with a heterogeneous biology, which has impeded the clinical assessment of patients. The currently-used clinically-based IPI provides useful information for treatment decision making, but has limited predictive power. Recent immunohistochemical approaches have identified two different prognostic groups: the more indolent germinal centre (GC)- and the higher risk activated B-cell (ABC)-like phenotypes. Although useful, prediction based on immunophenotype has limitations. The present study uses microRNA profiling and a number of well-characterised B-cell lymphoma cell lines to identify microRNA signatures that are correctly assigned to the DLBCL prognostic subgroups and distinguish DLBCL from other more indolent lymphoma, including follicular lymphoma (FL). MicroRNA microarray analysis was based on miRBase version 12.0 and analysis was performed using an unsupervised hierarchical clustering model. Discriminatory microRNAs were validated by qRT-PCR. We identified a 9 microRNA signature that discriminated between ABC- and GC-like DLBCL. This included 3 newly identified microRNAs, not previously associated with DLBCL and predicted to target genes that are de-regulated in lymphoma. DLBCL was distinguished from FL by 4 microRNAs and a total of 18 microRNAs were identified that differentiated between all lymphoma and control populations. Most of the discriminatory microRNAs have been reported previously to be known oncomiRs or act as tumour suppressors. In conclusion, the present study identified a microRNA signature that correctly classified GC and ABC phenotypes in DLBCL cell lines. This signature has yet to be assessed for prediction in clinical samples.
authors.affiliation: Academic Haematology, Northern Institute for Cancer Research, Newcastle University, Newcastle, Tyne and Wear, NE2 4HH, UK.
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Culpin
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Proctor
authors.forename: Brian
authors.initials: B
authors.lastname: Angus
authors.forename: Stephen
authors.initials: S
authors.lastname: Crosier
authors.forename: John J
authors.initials: JJ
authors.lastname: Anderson
authors.forename: Tryfonia
authors.initials: T
authors.lastname: Mainou-Fowler
mesh_terms: D018941:Antigens, CD19 / Q000378:metabolism; D001402:B-Lymphocytes / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D003937:Diagnosis, Differential; D020869:Gene Expression Profiling; D018858:Germinal Center / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008213:Lymphocyte Activation / Q000235:genetics; D016403:Lymphoma, Large B-Cell, Diffuse / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: D018941:Antigens, CD19; D035683:MicroRNAs