A Probabilistic Classification Tool for Genetic Subtypes of Diffuse Large B Cell Lymphoma with Therapeutic Implications.

The development of precision medicine approaches for diffuse large B cell lymphoma (DLBCL) is confounded by its pronounced genetic, phenotypic, and clinical heterogeneity. Recent multiplatform genomic studies revealed the existence of genetic subtypes of DLBCL using clustering methodologies. Here, we describe an algorithm that determines the probability that a patient's lymphoma belongs to one of seven genetic subtypes based on its genetic features. This classification reveals genetic similarities between these DLBCL subtypes and various indolent and extranodal lymphoma types, suggesting a shared pathogenesis. These genetic subtypes also have distinct gene expression profiles, immune microenvironments, and outcomes following immunochemotherapy. Functional analysis of genetic subtype models highlights distinct vulnerabilities to targeted therapy, supporting the use of this classification in precision medicine trials.
Competing Interests: Declaration of Interests G.W.W., D.W.H., and L.M.S. are inventors on an NIH patent application that is based on the work presented herein. D.W.S. was a consultant for Abbvie, Celgene, and Janssen; received research funding from NanoString Technologies, Janssen, and Roche/Genentech. Authors are included on additional patents, some of which are licensed by NanoString Technologies.
(Published by Elsevier Inc.)