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.

BCL6-translocations affect the phenotype of follicular lymphomas only in the absence of t(14;18)IgH/BCL2.

BACKGROUND: The translocation t(14;18)IgH/BCL2 is the molecular hallmark of follicular lymphomas (FL). A subset of cases harbours translocations involving the BCL6-gene locus. This study aimed to determine the frequency of BCL2- and BCL6-translocations in FL and to identify morphological and immuno-histochemical features with respect to the presence of BCL2- and BCL6-translocations. MATERIALS AND METHODS: Fluorescence-in-situ-hybridisation (FISH) was used to determine the BCL2- and BCL6-translocation status of 102 FL and these were compared to morphological and immunohistochemical parameters. RESULTS: Lymphomas with BCL6- and BCL2-translocations were very similar to t(14;18)-positive lymphomas without BCL6-translocations. In contrast, t(14;18)-negative lymphomas with BCL6-translocations were amongst others of higher grade, less often CD10-positive, involved the bone marrow less frequently and did not infiltrate the lymph node capsule. CONCLUSION: BCL2- and BCL6-translocations correlate with particular phenotypes of follicular lymphomas. BCL6-translocations seem to affect the phenotype only when they are not accompanied by BCL2-translocations.