The Molecular Oncohematology Research Group investigates the molecular pathogenesis of various hematological malignancies with a special focus on B-cell lymphomas.The main aim is to identify (epi)genetic biomarkers associated with therapy response and resistance. The goal of this translational research is to develop clinically applicable tools using advanced genomic technologies to support the individualization of therapies and molecular monitoring of patients with B-cell lymphomas.
B-cell lymphomas represent a heterogeneous group of diseases with an unmet clinical need for novel biomarkers guiding successful application of targeted therapies. The comprehensive genetic profiling of these diseases is however hampered by inability of the single biopsies used in routine diagnostics to capture the heterogeneity of the tumours. The use of plasma derived circulating tumour DNA (ctDNA) emerges as a promising non-invasive tool for accurate genomic profiling at diagnosis and for sensitive response evaluation including tracking the emerging resistant subclones. In this project, we will perform spatial and temporal mutation profiling using formalin-fixed, paraffin embedded (FFPE) tissue samples and ctDNA collected during the course of the disease in follicular lymphoma (FL), chronic lymphocytic leukemia (CLL) and primary central nervous system lymphoma (PCNSL) using next-generation sequencing (NGS). To identify epigenetic biomarkers associated with therapy resistance, single cell RNA-seq and single cell ATAC-seq will be performed on a subset of patients. Overall, these efforts will lead to development of clinically applicable NGS and droplet digital PCR (ddPCR) based genomic profiling and monitoring assays capturing the genetic heterogeneity of the patients supporting the more accurate risk stratification and individualization of therapies in B-cell lymphomas.