Genomic Taxonomy of Aggressive B-Cell Lymphoid Neoplasms

Aggressive B-cell lymphomas are a heterogeneous group of neoplasms, organized in the current classifications into more than 20 categories on the basis of morphology, immunophenotype, clinical presentation, and limited molecular features. Over the past 25 years, there has been an exponential accumulation of detailed genomic characterizations of these lymphomas. Many defined categories have been confirmed as relatively homogeneous, fulfilling the classification ideal of sharing core biological hallmarks. However, the largest group, diffuse large B-cell lymphoma, not otherwise specified, which makes up 70-74% of the patients, has been revealed to be remarkably heterogeneous at a genomic and biological level. In this review, we summarize the current state of knowledge and then propose an evolution of the classification of aggressive B-cell lymphomas to a genomics-informed taxonomy built around normal B-cell development and the different modes by which lymphomas achieve key hallmarks of cancer-hallmarks that can inform on patient management.