MicroRNA signatures in subtypes of follicular lymphoma

Background: MicroRNAs are regulators of gene expression implicated in vital cellular processes including differentiation, cell growth and apoptosis. Distinct microRNA signatures have been identified for many malignancies including follicular lymphoma (FL). However, no microRNA expression profile characteristic of FL subtypes, e.g. FL with B-cell lymphoma-6 (BCL6) locus rearrangement (FL^BCL2+/BCL6+, FL^BCL2-/BCL6+) or FL with diffuse growth pattern have been reported. Materials and Methods: MicroRNA signatures from 44 cases of FL were generated employing a quantitative real-time polymerase chain reaction approach. 15 cases of diffuse FL and 15 cases of FL^BCL2+/BCL6+/FL^BCL2-/BCL6+ were compared against 14 cases of typical FL^BCL2+/BCL6-. Results: Numerous microRNAs were found to be differentially expressed between FL^BCL2+/BCL6+ and FL^BCL2-/BCL6+, as well as diffuse FL, when compared to typical cases of FL. Up-regulation of several oncogenic microRNAs as well as down-regulation of tumor-suppressor microRNAs was identified. Cluster analysis, however, revealed no microRNA signatures distinct from the reference group for either subtype. Conclusion: These results indicate an involvement of microRNAs in the pathogenesis of FL and its subtypes. Marked de-regulation of oncogenic RNAs and tumor suppressors appears to correspond with a more aggressive phenotype frequently observed in FL^BCL2+/BCL6+, FL^BCL2-/BCL6+ and diffuse FL.