PhD thesis – Anders Petersen, 22 December 2011
On Friday 22 December 2011, MSc PhD student Anders Petersen, Department of Haematology, defended his PhD thesis with the title: “MicroRNA targets in Diffuse Large B-cell lymphoma”.
MicroRNAs are gene regulatory factors found to be differentially expressed in normal versus tumour tissue and between many different cancers and subgroups of cancers. MicroRNAs direct the binding of the RISC (RNA-inducing silencing complex) to the 3´UTR of specific mRNAs containing target sequences complementary to the microRNA. Thereby the RISC post transcriptional regulates the expression of this mRNA.
Diffuse Large B-Cell Lymphoma (DLBCL) has an incidence of approximately 2.9 per 100,000 people. It accounts for 30-40% of all non-Hodgkin lymphomas and it is a heterogeneous disease which can be divided into molecular subgroups on the basis of gene expression profiling (GEP).
This Ph.D. project has been focused on microRNA and mRNA differentially expressed between nodal and extranodal manifestation of DLBCL and the project has been divided into two parts. First, global microRNA expression analysis of 50 snap frozen tumours was performed in order to identify differentially expressed microRNAs between nodal (41) and extranodal (9) localizations of DLBCL.
The differentially expressed microRNAs were validated by QPCR and their significance in distinguishing nodal from extranodal localizations of DLBCL were tested in an additional set of 56 formalin fixed paraffin embedded (FFPE) tumours by QPCR. MiRNA expression of differentiated miRNA between nodal and extranodal localisation of DLBCL was correlated to survival. Second, identification of potential mRNA targets by bioinformatics correlations of global gene and microRNA expression analysis for the specific differentially expressed microRNAs found in part one was performed. Indirect and direct interactions between specific microRNAs and their potential targets were studied by knock down experiments, luciferace reporter assays and QPCR.
- Professor Charles H. Lawrie, PhD
Biodonostia Research Institute, San Sebastián
- Chief consultant Kirsten Grønbæk, DMSci
Dept. Hematology, Rigshospitalet, Copenhagen, Denmark
- Associate professor Steffen Junker, D.Phil. – chairman of the committee
Institute of Biomedicine, Aarhus University, Denmark
- Associate Professor, Karen Dybkær, Department of Haematology, Aalborg Hospital, Aarhus University, Denmark
- 22 December 2011, at 13.00 p.m.
- In the auditorium at Aalborg Science and Innovation Center, Aalborg Hospital, Aarhus University Hospital