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.

Figure 1

Hierarchical clustering of all samples based on the 38 miRNAs differentially expressed between BL and DLBCL. MiRNA-defined BL denotes the miRNA-defined group of BL cases, miR-DLBCL the group of miR-DLBCL cases. The hatched portion of the miR-DLBCL bar indicates the cases with intermediate miRNA expression features. MYC translocation: results from fluorescence in situ hybridization analysis (NA, not evaluable because of low tissue quality; negative, no translocation detectable with the probes described in the method section; positive, MYC translocation to either of the IG loci detectable). Diagnosis: according to the WHO criteria as described in the Patients and methods section.