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Review
. 2022 Nov 17:13:1237-1244.
doi: 10.18632/oncotarget.28309.

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

Daniel J Landsburg  1 , Jennifer J D Morrissette  1 , Stephen J Schuster  1 , Sunita D Nasta  1 , James N Gerson  1 , Stefan K Barta  1 , Jakub Svoboda  1 , Elise A Chong  1 , Megan S Lim  1
Affiliations
Review

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

Daniel J Landsburg et al. Oncotarget. .

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.

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

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Conflict of interest statement

CONFLICTS OF INTEREST

DJL – Research Funding: Curis, Triphase; Advisory Board Member: ADC Therapeutics, Calithera, Epizyme, Morphosys; Independent Data Monitoring Committee Member: Karyopharm. JJDM: none. SJS – Research funding: Celgene, Genetech/Roche, Incyte, Novartis, Abbvie, Adaptive Biotechnologies, DTRM, Juno Therapeutics, Merck, Pharmacyclics, TG Therapeutics; Consultancy: Acerta, Beigene, Celgene, Genetech/Roche, Incyte, Janssen, Legend Biotech, Loxo, Morphosys, MustangBio, Nordic, Nanovector, Novartis, Regeneron; Advisory Board Member: Regeneron. SDN – Research funding: Pharmacyclics, Roche, Rafael, FortySeven/Gilead. JNG – Research Funding: Loxo Oncology; Consultancy: Genetech, Abbvie. SKB – Consultancy: Affimed, Daiichi Sankyo, Kyowa Kirin; Independent Data Monitoring Committee Member: Janssen; Honoraria: Kyowa Kirin, Seagen, Acrotech. JS – Research Funding: Adaptive, Astra Zeneca, BMS, Incyte, Merck, Pharmacyclics, Seagen, TG Therapeutics; Advisory Board Member: Adaptive, Astra Zeneca, Incyte; Consultancy: Atara, BMS, Genmab, Pharamcyclics, Seagen. EAC – Consultancy: Novartis, Beigene, KITE, Tessa, Juno/BMS. MSL – Honoraria: EUSA Pharma.

Figures

Figure 1
Figure 1. Number and frequency of detected mutations of interest.
Figure 2
Figure 2
Mutation type and predicted impact of mutation on alteration of gene function for all mutations (A, B), CREBBP mutations (C, D), TP53 mutations (E, F) and EHZ2 mutations (G, H).
Figure 3
Figure 3. Tumor characteristics analyzed, by patient.
Figure 4
Figure 4
Disease free survival (A) and overall survival (B) for all patients; disease free survival (C) and overall survival (D) for all patients by CREBBP mutation status. Abbreviation: Mut: mutation.
See this image and copyright information in PMC

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References

    1. Lenz G, Wright G, Dave SS, Xiao W, Powell J, Zhao H, Xu W, Tan B, Goldschmidt N, Iqbal J, Vose J, Bast M, Fu K, et al., and Lymphoma/Leukemia Molecular Profiling Project. Stromal gene signatures in large-B-cell lymphomas. N Engl J Med. 2008; 359:2313–23. 10.1056/NEJMoa0802885. - DOI - PMC - PubMed
    1. Chapuy B, Stewart C, Dunford AJ, Kim J, Kamburov A, Redd RA, Lawrence MS, Roemer MGM, Li AJ, Ziepert M, Staiger AM, Wala JA, Ducar MD, et al.. Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes. Nat Med. 2018; 24:679–90. 10.1038/s41591-018-0016-8. - DOI - PMC - PubMed
    1. Schmitz R, Wright GW, Huang DW, Johnson CA, Phelan JD, Wang JQ, Roulland S, Kasbekar M, Young RM, Shaffer AL, Hodson DJ, Xiao W, Yu X, et al.. Genetics and Pathogenesis of Diffuse Large B-Cell Lymphoma. N Engl J Med. 2018; 378:1396–407. 10.1056/NEJMoa1801445. - DOI - PMC - PubMed
    1. Ennishi D, Jiang A, Boyle M, Collinge B, Grande BM, Ben-Neriah S, Rushton C, Tang J, Thomas N, Slack GW, Farinha P, Takata K, Miyata-Takata T, et al.. Double-Hit Gene Expression Signature Defines a Distinct Subgroup of Germinal Center B-Cell-Like Diffuse Large B-Cell Lymphoma. J Clin Oncol. 2019; 37:190–201. 10.1200/JCO.18.01583. - DOI - PMC - PubMed
    1. Sha C, Barrans S, Cucco F, Bentley MA, Care MA, Cummin T, Kennedy H, Thompson JS, Uddin R, Worrillow L, Chalkley R, van Hoppe M, Ahmed S, et al.. Molecular High-Grade B-Cell Lymphoma: Defining a Poor-Risk Group That Requires Different Approaches to Therapy. J Clin Oncol. 2019; 37:202–12. 10.1200/JCO.18.01314. - DOI - PMC - PubMed

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