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Lymphoma

Dysregulation of global microRNA expression in splenic marginal zone lymphoma and influence of chronic hepatitis C virus infection

Abstract

The precise molecular pathogenesis of splenic marginal zone lymphoma (SMZL) is still unknown. Clinical and epidemiological data suggest that chronic hepatitis C virus (HCV) infection may have an etiological role in a subset of cases.

We performed a large-scale microRNA (miRNA) expression profiling analysis of 381 miRNAs by quantitative reverse transcription PCR (Q-RT-PCR) of 26 microdissected splenic tissue samples (7 HCV+ SMZL; 8 HCV SMZL and 11 non-neoplastic splenic controls). Single assay Q-RT-PCR and miRNA in situ hybridization (miRNA-ISH) were used to confirm the results in an independent cohort. Unsupervised hierarchical clustering of miRNA expression profiles demonstrated a distinct signature of SMZL compared with the normal splenic marginal zone. Supervised analysis revealed differentially expressed miRNAs, including miRNAs with previously recognized tumor suppressive or oncogenic potential. Five miRNAs were found significantly overexpressed in SMZL, including miR-21, miR-155 and miR-146a, whereas seven miRNAs showed significantly reduced expression, including miR-139, miR-345, miR-125a and miR-126. Furthermore, we identified miR-26b, a miRNA known to have tumor suppressive properties, as significantly downregulated in SMZL arising in HCV-positive patients (P=0.0016). In conclusion, there is a characteristic dysregulation of miRNA expression in SMZL with a possible implication in its molecular tumorigenesis.

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Acknowledgements

We thank Janine Bronckhorst, Ekaterini Hadzoglou Sabine Albrecht and Ralf Lieberz for excellent technical assistance. This work was supported by the ‘Patenschaftsmodell’ grant from the medical faculty of the J.W. Goethe-University Hospital, Frankfurt, and by the Deutsche Forschungsgemeinschaft (GRK 1431/2, TR60, KFO129).

Authors Contribution

J Peveling-Oberhag: designed and performed research, revised and analyzed clinical data and wrote the manuscript; G Crisman performed research and collected and characterized histological samples; A Schmidt designed and performed research and assisted in the correction of the manuscript; C Döring performed bioinformatics and statistical analysis; M Lucioni provided advice and collected and characterized histological samples; L Arcaini provided advice and collected and revised clinical data; S Rattotti collected and revised clinical data; S Hartmann designed research, provided advice and collected and characterized histological samples; A Piiper provided advice and assisted in the correction of the paper; WP Hofmann designed research and assisted in the correction of the paper; M Paulli provided advice and collected and characterized histological samples; R Küppers designed research, provided advice and revised the manuscript; S Zeuzem designed research, provided advice and revised the paper and ML Hansmann designed research, collected and characterized histological samples and revised the paper.

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Peveling-Oberhag, J., Crisman, G., Schmidt, A. et al. Dysregulation of global microRNA expression in splenic marginal zone lymphoma and influence of chronic hepatitis C virus infection. Leukemia 26, 1654–1662 (2012). https://doi.org/10.1038/leu.2012.29

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