Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling

Diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgk in's lymphoma, is clinically heterogeneous: 40% of patients respond well to current therapy and have prolonged survival, whereas the remainder succumb to the disease. We proposed that this variability in natural history refle cts unrecognized molecular heterogeneity in the tumours, Using DNA microarr ays, we have conducted a systematic characterization of gene expression in B-cell malignancies. Here we show that there is diversity in gene expressio n among the tumours of DLBCL patients, apparently reflecting the variation in tumour proliferation rate, host response and differentiation state of th e tumour. We identified two molecularly distinct forms of DLBCL which had g ene expression patterns indicative of different stages of B-cell differenti ation. One type expressed genes characteristic of germinal centre B cells ( 'germinal centre B-like DLBCL'); the second type expressed genes normally i nduced during in vitro activation of peripheral blood B cells ('activated B -like DLBCL'), Patients with germinal centre B-like DLBCL had a significant ly better overall survival than those with activated B-like DLBCL, The mole cular classification of tumours on the basis of gene expression can thus id entify previously undetected and clinically significant subtypes of cancer.