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

Overview

Journal Cancer Cell

Publisher Cell Press

Specialty Oncology

Date 2020 Apr 15

PMID 32289277

Citations 447

Authors

George W Wright

Da Wei Huang

James D Phelan

Zana A Coulibaly

Sandrine Roulland

Ryan M Young

James Q Wang

Roland Schmitz

Ryan D Morin

Jeffrey Tang

Aixiang Jiang

Aleksander Bagaev

Olga Plotnikova

Nikita Kotlov

Calvin A Johnson

Wyndham H Wilson

David W Scott

Louis M Staudt

Affiliations

Soon will be listed here.

Abstract

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.

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