Using Informatics Tools to Identify Opportunities for Precision Medicine in Diffuse Large B-cell Lymphoma

Sharvil P. Patel, R. Andrew Harkins, Michelle J. Lee, Christopher R. Flowers, Jean L. Koff

Research output: Contribution to journalArticle

Abstract

Introduction: Diffuse large B-cell lymphoma (DLBCL) is genetically and clinically heterogeneous. Despite advances in genomic subtyping, standard frontline chemoimmunotherapy has remained unchanged for years. As high-throughput analysis becomes more accessible, characterizing drug–gene interactions in DLBCL could support patient-specific treatment strategies. Materials and Methods: From our systematic literature review, we compiled a comprehensive list of somatic mutations implicated in DLBCL. We extracted reported and primary sequencing data for these mutations and assessed their association with signaling pathways, cell-of-origin subtypes, and clinical outcomes. Results: Twenty-two targetable mutations present in ≥ 5% of patients with DLBCL were associated with unfavorable outcomes, yielding a predicted population of 31.7% of DLBCL cases with poor-risk disease and candidacy for targeted therapy. A second review identified 256 studies that had characterized the drug–gene interactions for these mutations via in vitro studies, mouse models, and/or clinical trials. Conclusions: Our novel approach linking the data from our systematic reviews with informatics tools identified high-risk DLBCL subgroups, DLBCL-specific drug–gene interactions, and potential populations for precision medicine trials. Despite advances in the genomic subtyping of diffuse large B-cell lymphoma (DLBCL), the standard frontline treatment has remained unchanged for years. A novel approach, linking a systematic review with informatics tools, identified high-risk DLBCL subgroups and DLBCL-specific drug–gene interactions. Twenty-two targetable mutations present in ≥ 5% DLBCL cases were associated with unfavorable outcomes, yielding a predicted population of 31.7% of DLBCL cases with poor-risk disease and candidacy for targeted therapy.

Original languageEnglish (US)
Pages (from-to)234-243.e10
JournalClinical Lymphoma, Myeloma and Leukemia
Volume20
Issue number4
DOIs
StatePublished - Apr 2020

Keywords

  • DLBCL
  • Drug–gene interactions
  • Genomics

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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