BIC and miR-155 Are Highly Expressed in Hodgkin, Primary Mediastinal and Diffuse Large B Cell Lymphomas.

In a previous study we demonstrated high expression of the non-coding BIC gene in the vast majority of Hodgkin’s lymphomas (HLs). It is now known that BIC is a primary microRNA (pri-miRNA) that can be processed to miRNA-155. We analyzed HL and NHL cell lines and tissue samples to determine miR-155 expression levels. High levels of miR-155 could be demonstrated in all HL tissue samples and most cell lines. Most NHL subtypes were negative for BIC as determined by RNA-ISH. However, 8/8 cases of primary mediastinal B cell lymphoma (PMBL) showed BIC staining in 12% of the tumor cells. QRT-PCR analysis confirmed high relative BIC levels (35). 12/18 cases of DLBCL showed a variable BIC staining with on average 7% of positive cells. Interestingly, activated B cell-like (ABC-like) DLBCL showed on average 12% of tumor cells positive for BIC while germinal centre B cell-like (GCB-like) DLBCL only showed on average 4% of cells positive for BIC. Differences in BIC expression levels were confirmed by qRT-PCR analysis revealing average BIC levels of 22 for ABC-like and 12 for GCB-like DLBCL. Northern blot analysis showed expression of miR-155 in all DLBCL and PMBL derived cell lines and tissue samples analyzed. In summary, we demonstrate expression of pri-miRNA BIC and its derivative miR-155 in HL, PMBL and DLBCL. In DLBCL, BIC expression is most pronounced in the ABC-like phenotype, possibly as a result of NF-κB activation.