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Lymphoma

The different epidemiologic subtypes of Burkitt lymphoma share a homogenous micro RNA profile distinct from diffuse large B-cell lymphoma

Abstract

Sporadic Burkitt lymphoma (sBL) can be delineated from diffuse large B-cell lymphoma (DLBCL) by a very homogeneous mRNA expression signature. However, it remained unclear whether all three BL variants—sBL, endemic BL (eBL) and human immunodeficiency virus-associated BL (HIV-BL)—represent a uniform biological entity despite their differences in geographical occurrence, association with immunodeficiency and/or incidence of Epstein–Barr virus (EBV) infection. To address this issue, we generated micro RNA (miRNA) profiles from 18 eBL, 31 sBL and 15 HIV-BL cases. In addition, we analyzed the miRNA expression of 86 DLBCL to determine whether miRNA profiles recapitulate the molecular differences between BL and DLBCL evidenced by mRNA profiling. A signature of 38 miRNAs containing MYC regulated and nuclear factor-kB pathway-associated miRNAs was obtained that differentiated BL from DLBCL. The miRNA profiles of sBL and eBL displayed only six differentially expressed miRNAs, whereas HIV and EBV infection had no impact on the miRNA profile of BL. In conclusion, miRNA profiling confirms that BL and DLBCL represent distinct lymphoma categories and demonstrates that the three BL variants are representatives of the same biological entity with only marginal miRNA expression differences between eBL and sBL.

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Acknowledgements

We would like to thank the German High Grade Lymphoma Study Group (DSHNL) for supporting this study and the pathologists of the German Reference Centers for Lymph Node Pathology for the panel review of the DLBCL included in the RiCOVER-60 study. We are also grateful to Korinna Jöhrens for evaluating the BL samples for generation of the tissue microarrays and Christoph Loddenkemper for evaluating immunohistochemical stainings. Furthermore, we thank E Berg, H Lammert and S Meier for excellent technical assistance. This work was supported by grants from the Deutsche Forschungsgemeinschaft (DFG) for the Transregio 54 (TRR54) the Fondazione Monte dei Paschi (MPS), the Kinderkrebsinitiative Buchholz / Holm-Seppensen and the Deutsche Krebshilfe.

Author contributions

DL: analyzed and interpreted data, designed research, wrote the paper; LL: initiated and planned the study, designed research, interpreted data, wrote the paper; MH: interpreted data, designed research, wrote the paper; SV: performed statistical analysis; HH, CGL, JP, TA, GDF: performed research; JG, JN, ER, MP: contributed vital new reagents; GO, AR, RS: analyzed and interpreted data; CC: contributed analytical tools; HS: initiated the study, designed research, interpreted data, wrote the paper.

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Correspondence to D Lenze.

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Lenze, D., Leoncini, L., Hummel, M. et al. The different epidemiologic subtypes of Burkitt lymphoma share a homogenous micro RNA profile distinct from diffuse large B-cell lymphoma. Leukemia 25, 1869–1876 (2011). https://doi.org/10.1038/leu.2011.156

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