MicroRNA Profiling In Activated B-Cell and Germinal Center B-Cell Diffuse Large B-Cell Lymphoma Using Formalin Fixed, Paraffin Embedded Patient Biopsies

Abstract

AbstractAbstract 3111Diffuse Large B cell lymphoma (DLBCL) is the most common form of non-Hodgkin's lymphoma. The Leukemia Lymphoma Molecular Profiling Project (LLMPP) collaboration has done extensive work regarding this disease including gene expression profiling to show that the cell of origin impacts the prognosis of the patient. Those cases which arise from an activated B cell (ABC) have a worse prognosis than those cases which arise from a germinal center B cell (GCB). We have used a subset of cases from our institution which have had gene expression profiling performed on frozen material and assigned ABC (n=18) or GCB (n=24) status (Rosenwald et al NEJM 2002, 346:1937). We have used matched formalin fixed paraffin embedded (FFPE) tissue block from these cases to obtain a microRNA profile utilizing the qNPA technology (High ThroughPut Genomics) as previously published (Roberts et al Lab Invest 2007, 87:979). This novel FFPE based RNAase protection assay measured 688 human microRNAs. Each microRNA was represented twice on the array and the values averaged for a signal value. The data were normalized to the total signal of the microarray. We were able to define a signature of increased microRNA for each DLBCL subtype as shown in Table 1.ABC subtypeGCB subtypehsa-miR-155hsa-miR-28-5phsa-miR-196ahsa-miR-138hsa-miR-501-3phsa-miR-151-3phsa-miR-656hsa-miR-151-5phsa-miR-1247hsa-miR-182hsa-miR-210hsa-miR-613The hsa-miR-155 is of importance in lymphoma as it regulates the generation of immunoglobulin class-switch in plasma cells (Turner et al Immunity 2007, 27:847) and was previously identified as a characteristic of ABC cell lines (Lossos et al Blood 2009,113:3754). The hsa-miR-210 has been shown to modulate the MYC antagonist MNT which allows for MYC expression (Grandori et all Cell Cycle 2009, 8:2756). This microRNA profile provides an opportunity to further explore the role microRNA plays in lymphoma biology and in particular, in DLBCL subtype determination. The success of the technique in FFPE tissue holds promise for further microRNA studies on archival material. Disclosures:No relevant conflicts of interest to declare.