Comparative molecular cell-of-origin classification of diffuse large B-cell lymphoma based on liquid and tissue biopsies

Abstract

Diffuse large B-cell lymphoma (DLBCL) is a heterogenous blood cancer, but can be broadly classified into two main subtypes, germinal center B-cell-like (GCB) and activated B-cell-like (ABC). GCB and ABC subtypes have very different clinical courses, with ABC having a much worse survival prognosis. It has been observed that patients with different subtypes also respond differently to therapeutic intervention, in fact, some have argued that ABC and GCB can be thought of as separate diseases altogether. Due to this variability in response to therapy, having an assay to determine DLBCL subtypes has important implications in guiding the clinical approach to the use of existing therapies, as well as in the development of new drugs. The current gold standard assay for subtyping DLBCL uses gene expression profiling on formalin fixed, paraffin embedded (FFPE) tissue to determine the “cell of origin” and thus disease subtype. However, this approach has some significant clinical limitations in that it 1) requires a biopsy 2) requires a complex, expensive and time-consuming analytical approach and 3) does not classify all DLBCL patients.