Work

Whole-exome analysis reveals novel somatic genomic alterations associated with cell of origin in diffuse large B-cell lymphoma

Year: 2017

Type: article

Abstract: Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma, with an estimated 27 650 cases diagnosed in 2016. 1 Gene expression profiling has identified three subtypes of DLBCL; germinal center B-Cell like (GCB), activated B-cell like (ABC) and primary mediastinal B-cell lymphoma (PMBL). 2 This molecular heterogeneity is indicative of a unique cell of origin (COO) giving rise to each subtype and is associated with clinical outcome, with treatment, leading to remission in ~80% of GCB patients but only ~50% in ABC patients. 3 The poor prognosis of ABC-DLBCL is distinguished by constitutive activity of the NF-κB pathway, 4 which has also been associated with drug resistance in all subtypes of DLBCL. 5 However, heterogeneity remains an issue within COO subtypes and there is a need for further classification in the current era of COO-specific therapeutic targeting. Sequencing of DLBCL tumors has identified a panel of mutations that associate with COO, however, much of this work was performed using limited gene panels or traditional Sanger sequencing methods across multiple patient cohorts. Furthermore, most previous studies defined COO using the Hans method, which only has ~80% concordance with gene expression profiling. 6 A comprehensive genomic analysis of COO, including both mutations and copy number analysis, on a clinically defined set of DLBCL cases with accurate COO has not been performed.

Source: Blood Cancer Journal

DOI: 10.1038/bcj.2017.33