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.


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.


CONCLUSIONS
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.
Institut für Pathologie, Referenzzentrum für Lymphknotendiagnostik und Hämatopathologie, Universität zu Lübeck, 23538 Lübeck, Deutschland. niklas.gebauer@medizin.uni-luebeck.de.
Niklas
N
Gebauer
Wiebke
W
Gollub
Björn
B
Stassek
Veronica
V
Bernard
Dirk
D
Rades
Alfred C
AC
Feller
Christoph
C
Thorns
D004268:DNA-Binding Proteins / Q000235:genetics; D019254:Genes, bcl-2; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008224:Lymphoma, Follicular / Q000235:genetics*; D035683:MicroRNAs / Q000032:analysis / Q000235:genetics*; D051560:Proto-Oncogene Proteins c-bcl-6; D060888:Real-Time Polymerase Chain Reaction; D059467:Transcriptome / Q000235:genetics*; D014178:Translocation, Genetic
C084103:BCL6 protein, human; D004268:DNA-Binding Proteins; D035683:MicroRNAs; D051560:Proto-Oncogene Proteins c-bcl-6
BCL2; BCL6; MicroRNAs; follicular lymphoma