PhD ceremony Mr. J.L. Robertus: MicroRNA profiling in B cell non-Hodgkin Lymphoma: focus on the role of MYC

PhD ceremony: Mr. J.L. Robertus, 11.00 uur, Academiegebouw, Broerstraat 5, Groningen

Dissertation: MicroRNA profiling in B cell non-Hodgkin Lymphoma: focus on the role of MYC

Promotor(s): prof. J.H.M. van den Berg, prof. P.M. Kluin

Faculty: Medical Sciences

Most non-Hodgkin lymphoma (NHL) subtypes are characterized by specific chromosomal aberrations and aberrant gene expression patterns, some of which have been shown to be particularly relevant to their pathogenesis. In the past decade, research on microRNAs (miRNAs) has further contributed to knowledge about the pathogenesis of NHL, but the picture is far from complete. MiRNAs are a group of regulatory small RNAs that belong to the non-coding RNA family. MiRNAs can post-trancriptionally regulate the expression of their target genes, which include oncogenes and tumor suppressor genes, and as such contribute to tumorigenesis. Studies on miRNAs might therefore further improve our understanding of the molecular abnormalities that underlie the pathogenesis of lymphomas and cancer in general. This thesis focused on the role of miRNAs in the pathogenesis of lymphomas, in particular that of diffuse large B cell lymphoma (DLBCL) and Burkitt lymphoma (BL). We identified two miRNAs that characterize the testicular and CNS DLBCL cases. We further showed marked differences in the expression pattern of the oncogenic miRNA cluster, miR-17~92 with miR-92 being the most abundant miRNA in most cases, and miR-19b being the most significantly induced miRNA as compared to their normal counterparts. We further established specific miRNA expression profiles in different NHL subtypes and showed that the profile of BL is strongly defined by MYC. Finally, we identified seven MYC regulated miRNAs that have a remarkably strong impact on growth of BL cells.