[1288] Analyses of Micro-RNA Expression in Classical Hodgkin Lymphoma Tumors

B Sanchez-Espiridion, J Alves-ferreira, M Canales, ME Rodriguez, MM Morente, MA Piris, JF Garcia. Spanish National Cancer Centre, Madrid, Spain; Hospital La Paz, Madrid, Spain; MD Anderson International, Madrid, Spain

Background: Micro-RNAs (miRNAs) are small non-coding RNAs which regulate the expression of multiple target mRNAs, playing a key role in the control of the different biological processes implicated in cancer pathogenesis. Initial studies are showing that miRNA losses and gains may explain some of the biological and clinical features of different lymphoma types, and recent analyses of miRNA expression in classical Hodgkin Lymphoma (cHL) cells and tumors have also demonstrated deregulated expression of some miRNAs.
Design: To further analyze the implication of miRNAs in the pathogenesis of cHL, we have profiled miRNA in a series of advanced cHL patients and cell lines, including 29 fresh frozen lymph samples of cHL whose clinical data were availble. As controls, 4 fresh frozen lymph nodes and 4 fresh frozen tonsils were used. We also analyzed miRNA profiles from five cHL-derived cell lines (L-540,L-1236,L-428,HDLM-2 and KMH-2) allowing us to characterize microRNA signatures corresponding to tumor HRS cells and their reactive cell microenvironment. Hybridization was done using total RNA with Agilent 8x15K Human miRNA Microarray Kit v.2 for detection of 723 human and 76 human viral microRNAs (Agilent Technologies).
Results: We identified 123 miRNAs differentially expressed between cHL tumors and controls (37 upregulated and 86 downregulated miRNAs in tumor samples). Some of the most downregulated (miR-31, miR-5905p, miR-285p,) and upregulated (hsa-miR-220c, hsa-miR-526b, hsa-miR-495) miRNAs have been previously related to other cancer types. Targets of these miRNAs included some of the genes identified as deregulated in cHL, like CHEK1, BUB1, CDK9 (involved in mitotic chekpoint regulation) and some transcription factors such us E2F. Interestingly, the miRNA signature in cHL also included some EBV-encoded miRNAs (upregulation of miR-BART12 and downregulation of miR-BHRF1-3) potentially associated with the viral latency status and that may serve as an immunomodulatory mechanism in the tumors. In addition, the availability of clinical data allowed us to identify a set of miRNA with prognostic and predictive capacity in advanced cHL.
Conclusions: Our results suggest possible roles of human miR-31, miR-590, miR-220c, hsa-miR-526b, and viral (EBV-encoded) miR-BART12; miR-BHRF1-3 in the pathogenesis of cHL. These results will be validated in an additional series of patients using RT-PCR paraffin embedded samples.
Category: Hematopathology

Wednesday, March 11, 2009 9:30 AM

Poster Session V # 196, Wednesday Morning