Mantle cell Lymphoma (MCL) is a rare B cell malignancy with a disease course varying from indolent cases that can initially be followed without therapy, to highly aggressive variants with short survival despite treatment with intensified chemoimmunotherapy. Therefore, the development of prognostic biomarkers to support clinical decision making is highly warranted. 

Circular RNAs (circRNAs) are highly stable non-coding RNA molecules with tissue-specific expression that are emerging as promising biomarkers and might be implicated in the development of cancer. 

The aim of this phD thesis was to profile circRNA expression patterns in MCL and other B-cell malignancies, and to examine the prognostic significance of circRNAs in the heterogenic disease MCL. 

As no methodologies for accurate quantification of circRNAs in clinical samples were available beforehand, we identify the Nanostring nCounter technology as a specific and sensitive methodology for circRNA quantification compatible with use of archival tumor samples from patients. 

Using Nanostring, we quantified selected circRNAs in MCL using samples from two uniformly treated and independent patient cohorts from the clinical trials MCL2 and MCL3. We show that nine circRNAs incorporated into a single signature, circSCORE is highly predi tive of outcome in these cohorts, and thus serves as a promising novel biomarker in MCL. 

Mette Dahl, cand.med. 

12th of February, Department of Clinical Medicine, University of Copenhagen