Exome and targeted sequencing in clinical oncology—Use diffuse large B-cell lymphoma as a model in oncology practice

Abstract

Diffuse large B-cell lymphoma (DLBCL) is a highly heterogeneous lymphoid neoplasm with variations in gene expression profiles and genetic alterations, which lead to substantial variations in clinical course and response to treatment. The advent of high-throughput genome sequencing platforms, and especially whole-exome sequencing, has helped to define the genetic landscape of DLBCL. In the past decade, these studies have identified many genetic alterations in DLBCL, some of which are specific to B cell lymphomas, whereas others can also be observed in other types of cancer. These aberrations result in altered activation of a wide range of signaling pathways and other cellular processes, including those involved in B cell differentiation, B cell receptor signaling, activation of the NF-κB pathway and epigenetic regulation. Further elaboration of the genetics of DLBCL will not only improve our understanding of disease pathogenesis but also provide further insight into disease classification, prognostication and therapeutic targets. In this review, we describe the current understanding of the prevalence and causes of specific genetic alterations in DLBCL and their role in disease development and progression. We also summarize the available clinical data on therapies designed to target the aberrant pathways driven by these alterations.