Oncotarget

Research Papers:

Mutation analysis performed on tumor biopsies from patients with newly-diagnosed germinal center aggressive B cell lymphomas

Daniel J. Landsburg _, Jennifer J.D. Morrissette, Stephen J. Schuster, Sunita D. Nasta, James N. Gerson, Stefan K. Barta, Jakub Svoboda, Elise A. Chong and Megan S. Lim

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Oncotarget. 2022; 13:1237-1244. https://doi.org/10.18632/oncotarget.28309

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Abstract

Daniel J. Landsburg1, Jennifer J.D. Morrissette1, Stephen J. Schuster1, Sunita D. Nasta1, James N. Gerson1, Stefan K. Barta1, Jakub Svoboda1, Elise A. Chong1 and Megan S. Lim1

1 Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA

Correspondence to:

Daniel J. Landsburg, email: daniel.landsburg@pennmedicine.upenn.edu

Keywords: diffuse large B cell lymphoma; high grade B cell lymphoma; mutation analysis; next generation sequencing; chemotherapy

Received: September 15, 2022     Accepted: October 12, 2022     Published: November 17, 2022

Copyright: © 2022 Landsburg et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ABSTRACT

Comprehensive genomic analyses of tumor biopsies from patients with newly-diagnosed germinal center B cell (GCB) diffuse large B cell/high grade B cell lymphoma (DLBCL/HGBL) have identified molecular subtypes predictive of inferior survival, which are characterized by somatic mutations that can be detected through clinical laboratory mutation analysis (CLMA). To determine the frequency and predictive value of individual genetic mutations associated with these experimentally-defined poor-risk subgroups, we reviewed the findings from CLMA performed on tumors from patients with newly-diagnosed GCB DLBCL/HGBL who were previously treated at our institution. CLMA was successfully performed on 58/59 patient tumor biopsies with a median turnaround time of 16 days, and 51 on which CLMA was routinely performed with adequate clinical follow-up were analyzed. Patients whose tumors demonstrated CREBBP mutation experienced a lower estimated rate of 2-year disease free survival (DFS) as compared to those whose tumors did not (45% [95% CI 18–68%] vs. 67% [95% CI 44–83%], P = 0.045). CREBBP mutations may be frequent and predict for inferior DFS in patients with newly-diagnosed GCB DLBCL/HGBL. Furthermore, CLMA may be practically-applied to translate experimental findings into those with more direct application to risk stratification and clinical trial design in subsets of patients with DLBCL/HGBL.


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