Circulating Tumor DNA Measurements As Early Outcome Predictors in Diffuse Large B-Cell Lymphoma

Kurtz, David M.; Scherer, Florian; Jin, Michael C.; Soo, Joanne; Craig, Alexander; Esfahani, Mohammad Shahrokh; Chabon, Jacob J.; Stehr, Henning; Liu, Chih Long; Tibshirani, Robert; Maeda, Lauren S.; Gupta, Neel K.; Khodadoust, Michael S.; Advani, Ranjana H.; Levy, Ronald; Newman, Aaron M.; Dührsen, Ulrich; Hüttmann, Andreas; Meignan, Michel; Casasnovas, René Olivier; Westin, Jason R.; Roschewski, Mark; Wilson, Wyndham H.; Gaïdano, Gianluca; Rossi, Davide; Diehn, Maximilian; Alizadeh, Ash A.

doi:10.1200/jco.2018.78.5246

Cited by 362 publications

(431 citation statements)

References 32 publications

Supporting

Mentioning

398

Contrasting

Unclassified

Order By: Relevance

“…Kurtz et al 26 13 In the current study, TP53 CHIP-carrying clone in one patient with DLBCL decreased in size at the time of developing ANKL. TP53 mutation was reportedly observed in only one of 14 ANKL patients in an exome-wide sequencing study.…”

Section: Discussionsupporting

confidence: 49%

Mutations found in cell‐free DNAs of patients with malignant lymphoma at remission can derive from clonal hematopoiesis

et al. 2019

View full text Add to dashboard Cite

Cell‐free DNA (cfDNA) analysis to detect circulating tumor DNA has been focused on monitoring malignant lymphomas. However, clonal hematopoiesis of indeterminate potential (CHIP)‐associated mutations can also be detected by cfDNA analysis. Our aim is to investigate the origin of mutations detected in cfDNA among B‐cell lymphoma patients. MYD88/CD79B, DNMT3A, and TP53 were chosen as genes of interest, representing each of the following categories: lymphoma driver genes, CHIP‐related genes, and genes shared between lymphoma and CHIP. Seventy‐five B‐cell lymphoma patients were included in this retrospective study. Serum cfDNAs at time of complete metabolic response (CMR) were sequenced for TP53 (N = 75) and DNMT3A (N = 49). MYD88 p.L265P and CD79B p.Y196C/H mutations were analyzed in diffuse large B‐cell lymphoma (DLBCL) patients whose tumor samples were available (N = 29). Two and seven mutations in TP53 and DNMT3A, respectively, were detected in cfDNA at CMR. These mutations were detected in either bone marrow mononuclear cells (BMMC) or PBMC. Although four DNMT3A mutations were also detected in tumors, median variant allele frequencies in the tumors (<1.0%) were significantly lower than those in both BMMC (6.1%) and serum (5.2%) obtained before the therapy. Conversely, five MYD88 and three CD79B mutations detected in tumors were confirmed in cfDNA before therapy, but not in BMMC nor in cfDNA at CMR. Thus, all TP53 and DNMT3A mutations detected in cfDNA at remission seemed to originate from CHIP rather than from residual disease. Results of liquid biopsy should be carefully interpreted, especially in genes shared between lymphomas and CHIP.

show abstract

Section: Discussionsupporting

confidence: 49%

Mutations found in cell‐free DNAs of patients with malignant lymphoma at remission can derive from clonal hematopoiesis

et al. 2019

View full text Add to dashboard Cite

show abstract

“…From a precision medicine perspective, cfDNA genotyping may assist clinicians in choosing the most suitable option for targeted therapy through facilitated detection of individual genetic subclones responsible for relapse in DLBCL patients. There are other recent studies that evaluated plasma cfDNA levels in DLBCL (Kurtz et al, 2018), addressing whether it can predict or monitor therapy response or if it can predict tumor burden or prognosis of FL cases (Delfau-Larue et al, 2018). Using droplet digital PCR, Alcaide et al detected previously known mutations (e.g., EZH2 Y641 and STAT6 D419) in circulating tumor DNA in major B cell NHL subtypes (Alcaide et al, 2016).…”

Section: Noninvasive Clinical Applications Of Genomic Alterations Of mentioning

confidence: 99%

Genetic alterations in B cell lymphoma subtypes as potential biomarkers for non-invasive diagnosis, prognosis, therapy, and disease monitoring

Sönmez

Küçük

2020

Turk J Biol

View full text Add to dashboard Cite

Neoplastic transformation of germinal center B (GCB) cells may give rise to a variety of different B cell lymphoma subtypes, most of which show substantial heterogeneity in terms of genetic alterations and clinical features. The mutations observed in cancerrelated genes in GCB cells are related to abnormalities in the immunogenetic mechanisms associated with germinal center reaction. Recent studies have rapidly identified genomic alterations in B cell lymphomas that may be useful for better subclassification, noninvasive diagnosis, and prediction of response to therapy. The WHO recognizes different lymphoma subsets classified within 2 major categories of B cell lymphoma: Hodgkin's lymphoma (HL) and B cell non-Hodgkin's lymphoma (NHL), each with distinct genetic aberrations, including chromosomal translocations, copy number abnormalities, or point mutations. Next-generation sequencing-based technologies have allowed cancer researchers to identify somatic mutations and gene expression signatures at a rapid pace so that novel diagnostic or prognostic biomarkers, as well as therapeutic targets, can be discovered much faster than before. Indeed, deep sequencing studies have recently revealed that lymphoma-specific somatic mutations may be detected in cell-free circulating DNA obtained from the peripheral blood of B cell lymphoma patients, suggesting the possibility of minimally invasive diagnosis, monitoring, and predicting response to therapy of B cell lymphoma patients. In this study, the current status of the recurrent genetic aberrations observed during diagnosis and/ or relapse in HL and the major subtypes of B cell NHL (i.e. diffuse large B cell lymphoma, follicular lymphoma, mantle cell lymphoma, and Burkitt lymphoma) are discussed to shed light on their potential use as noninvasive diagnostic or prognostic biomarkers and to reveal their role in lymphomagenesis as a target in therapy for newly diagnosed and chemotherapy-resistant cases.

show abstract

“…Circulating tumor DNA can be used in numerous ways to improve the management and characterization of both indolent and aggressive NHL (Table ). The application with immediate clinical implications involves replacing surveillance imaging with surveillance monitoring of ctDNA for detection of early relapse in DLBCL . The lead‐time offered by ctDNA monitoring creates a “window of opportunity” in which earlier institution of salvage therapy can be considered (Figure ).…”

Section: Clinical Applications Of Circulating Tumor Dnamentioning

confidence: 99%

“…Pretreatment ctDNA may also capture critical biologic information. Multiple studies have shown that pretreatment ctDNA levels in DLBCL correlate with markers of tumor burden such as advanced stage, LDH, and the international prognostic index (IPI) score . It is not clear, however, if other biologic processes affect pretreatment ctDNA levels.…”

Section: Clinical Applications Of Circulating Tumor Dnamentioning

confidence: 99%

See 1 more Smart Citation

Liquid biopsy in non‐Hodgkin's lymphoma

Melani

Wilson

Roschewski

2019

Hematological Oncology

Self Cite

View full text Add to dashboard Cite

ctDNA provides an important new strategy that will aid in the treatment of non-Hodgkin's lymphoma. Immunoglobulin sequencing provides a tumor specific marker for disease activity with a sensitivity equivalent to one tumor cell per 10-6. Furthermore, it can provide an estimate of tumor bulk and tumor response dynamics during treatment.Interim monitoring can identify patients at high risk of treatment failure and surveillance monitoring can identify patients months before radiographic disease progression. Tumor specific mutations can also be detected in ctDNA and may reflect an averaging of mutations present within multiple tumor masses. Such analysis may aid in the molecular characterization of tumors and selection of targeted treatments for precision medicine. Hematological Oncology. 2019;37(S1):70-74.wileyonlinelibrary.com/journal/hon

show abstract

Circulating Tumor DNA Measurements As Early Outcome Predictors in Diffuse Large B-Cell Lymphoma

Abstract: Pretreatment ctDNA levels and molecular responses are independently prognostic of outcomes in aggressive lymphomas. These risk factors could potentially guide future personalized risk-directed approaches.

Cited by 362 publications

References 32 publications

Mutations found in cell‐free DNAs of patients with malignant lymphoma at remission can derive from clonal hematopoiesis

Mutations found in cell‐free DNAs of patients with malignant lymphoma at remission can derive from clonal hematopoiesis

Genetic alterations in B cell lymphoma subtypes as potential biomarkers for non-invasive diagnosis, prognosis, therapy, and disease monitoring

Liquid biopsy in non‐Hodgkin's lymphoma

Contact Info

Product

Resources

About