Molecular Pathogenesis and Therapeutic Response of Diffuse Large B Cell Lymphoma Genetic Subtypes

Diffuse large B cell lymphoma (DLBCL) is a clinically and genetically heterogeneous disease. Molecular profiling studies in DLBCL have identified three distinct disease subtypes using gene expression profiling, whereas mutation analysis of tumors has identified at least six separate subtypes. Although each classifier predicts clinical responses to immunochemotherapy and targeted therapies, molecular profiling is not universally performed or uniformly implemented. In this review, we focus on the biology of the LymphGen algorithm defined genetic subtypes revealed by genomic, transcriptomic, and single-cell profiling. We highlight recent advances in understanding the major drivers of disease and discuss how different mutations promote common hallmarks of cancer that are vulnerable to precision medicine agents.