TY - JOUR
T1 - Using Informatics Tools to Identify Opportunities for Precision Medicine in Diffuse Large B-cell Lymphoma
AU - Patel, Sharvil P.
AU - Harkins, R. Andrew
AU - Lee, Michelle J.
AU - Flowers, Christopher R.
AU - Koff, Jean L.
N1 - Publisher Copyright:
© 2020 Elsevier Inc.
PY - 2020/4
Y1 - 2020/4
N2 - 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.
AB - 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.
KW - DLBCL
KW - Drug–gene interactions
KW - Genomics
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U2 - 10.1016/j.clml.2019.12.003
DO - 10.1016/j.clml.2019.12.003
M3 - Article
C2 - 32063526
AN - SCOPUS:85079379001
SN - 2152-2650
VL - 20
SP - 234-243.e10
JO - Clinical Lymphoma, Myeloma and Leukemia
JF - Clinical Lymphoma, Myeloma and Leukemia
IS - 4
ER -