Oncotarget | Mutation Analysis Performed on Tumor Biopsies From Patients With Newly-Diagnosed Germinal Center Aggressive B Cell Lymphomas

“Our analysis demonstrates that the presence of CREBBP mutations in tumor biopsies from patients with newly-diagnosed GCB DLBCL/HGBL is associated with poorer DFS [disease free survival] following treatment with front-line immunochemotherapy.”

BUFFALO, NY- November 17, 2022 – A new research paper was published in Oncotarget's Volume 13 on November 17, 2022, entitled, “Mutation analysis performed on tumor biopsies from patients with newly-diagnosed germinal center aggressive B cell lymphomas.”

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, researchers 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 from the University of Pennsylvania reviewed the findings from CLMA performed on tumors from patients with newly-diagnosed GCB DLBCL/HGBL who were previously treated at the University of Pennsylvania. 

“Thus, we sought to analyze the results of CLMA performed at our institution on tumors from patients with newly-diagnosed GCB DLBCL/HGBL previously-treated with first line immunochemotherapy to determine the frequency and predictive value of the presence of individual genetic mutations associated with these experimentally-defined poor-risk subgroups.”

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). The researchers note that 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.

“In conclusion, CLMA performed on tumor biopsies from patients with newly-diagnosed GCB DLBCL/HGBL revealed frequent mutations in CREBBP which were predicted to result in loss of function as well as a significantly lower rate of estimated DFS at 2 years.”

DOI: https://doi.org/10.18632/oncotarget.28309 

Correspondence to: Daniel J. Landsburg - daniel.landsburg@pennmedicine.upenn.edu 

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

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