Somatic mutations of cell-free circulating DNA detected by next-generation sequencing reflect the genetic changes in both germinal center B-cell-like and activated B-cell-like diffuse large B-cell lymphomas at the time of diagnosis

Bohers, Élodie; Viailly, Pierre-Julien; Dubois, Sydney; Bertrand, Philìppe; Maingonnat, Catherine; Mareschal, Sylvain; Ruminy, Philippe; Picquenot, Jean‐Michel; Bastard, Christian; Desmots, Fabienne; Fest, Thierry; Leroy, Karen; Tilly, Hervé; Jardin, Fabrice

doi:10.3324/haematol.2015.123612

Cited by 70 publications

(60 citation statements)

References 14 publications

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“…Furthermore, although this study was performed on frozen tumor samples, which are of limited availability, the Lymphopanel was designed to be effective in FFPE samples as well, further cementing its capacity to play an essential role in clinical disease management. In addition, our team has recently demonstrated that Lymphopanel NGS can be successfully performed using plasma-extracted cell-free circulating DNA, highlighting its feasibility and potential role in the monitoring of DLBCL (52). Taken together, these results serve as proof-of-principle that NGS with a consensus gene panel can alter the manner in which DLBCL patients are subclassified and treated.…”

Section: Identification Of Gene Mutations Correlated With Clinical Chmentioning

confidence: 63%

Next-Generation Sequencing in Diffuse Large B-Cell Lymphoma Highlights Molecular Divergence and Therapeutic Opportunities: a LYSA Study

Dubois

Viailly

Mareschal

et al. 2016

Clinical Cancer Research

179

155

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Purpose: Next-generation sequencing (NGS) has detailed the genomic characterization of diffuse large B-cell lymphoma (DLBCL) by identifying recurrent somatic mutations. We set out to design a clinically feasible NGS panel focusing on genes whose mutations hold potential therapeutic impact. Furthermore, for the first time, we evaluated the prognostic value of these mutations in prospective clinical trials.Experimental Design: A Lymphopanel was designed to identify mutations in 34 genes, selected according to literature and a whole exome sequencing study of relapsed/refractory DLBCL patients. The tumor DNA of 215 patients with CD20þ de novo DLBCL in the prospective, multicenter, and randomized LNH-03B LYSA clinical trials was sequenced to deep, uniform coverage with the Lymphopanel. Cell-of-origin molecular classification was obtained through gene expression profiling with HGU133þ2.0 Affymetrix GeneChip arrays. Results:The Lymphopanel was informative for 96% of patients. A clear depiction of DLBCL subtype molecular heterogeneity was uncovered with the Lymphopanel, confirming that activated B-celllike (ABC), germinal center B-cell like (GCB), and primary mediastinal B-cell lymphoma (PMBL) are frequently affected by mutations in NF-kB, epigenetic, and JAK-STAT pathways, respectively. Novel truncating immunity pathway, ITPKB, MFHAS1, and XPO1 mutations were identified as highly enriched in PMBL. Notably, TNFAIP3 and GNA13 mutations in ABC patients treated with R-CHOP were associated with significantly less favorable prognoses.Conclusions: This study demonstrates the contribution of NGS with a consensus gene panel to personalized therapy in DLBCL, highlighting the molecular heterogeneity of subtypes and identifying somatic mutations with therapeutic and prognostic impact.

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Section: Identification Of Gene Mutations Correlated With Clinical Chmentioning

confidence: 63%

Next-Generation Sequencing in Diffuse Large B-Cell Lymphoma Highlights Molecular Divergence and Therapeutic Opportunities: a LYSA Study

Dubois

Viailly

Mareschal

et al. 2016

Clinical Cancer Research

179

155

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“…[10][11][12] Because ctDNA derives from tumor tissue, it is a highly specific tumor biomarker. 13 It is present without detectable circulating tumor cells and correlates with tumor burden in early-and late-stage malignancies. 14,15 Assays designed for molecular monitoring must accurately discriminate ctDNA from DNA that originates in nonmalignant tissue.…”

Section: Technical Aspects Of Ctdnamentioning

confidence: 99%

Dynamic monitoring of circulating tumor DNA in non-Hodgkin lymphoma

Roschewski

Staudt

Wilson

2016

Blood

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Response assessment in lymphoma relies on imaging scans that do not capture biologic processes at the molecular level. Monitoring circulating tumor DNA (ctDNA) with next-generation sequencing–based assays can detect recurrent disease prior to scans and “liquid biopsies” for somatic mutations address tumor heterogeneity, clonal evolution, and mechanisms of resistance to guide precision treatment. Preanalytic collection and processing procedures should be validated and standardized. We describe emerging applications of ctDNA monitoring including real-time analysis of tumor dynamics, preclinical disease detection, and precision-directed treatment paradigms.

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“…They analyzed mutations in ctDNA and tissue. The single nucleotide variants were identified in genes that defined ABC-Like (MYD88, CD79A/B, PRDM1, CARD 11, IRF4) and GCBLike (EZH2, BCL2, GNA13, TNFSRF14) DLBCL subtypes [65]. It was possible to quantify MRD in plasma ccfDNA in DLBCL and Primary Mediastinal B-Cell Lymphoma (PMBL) patients.…”

Section: Non-hodgkin Lymphomas (Nhl)mentioning

confidence: 99%

Liquid Biopsy in Liquid Tumors

Ranuncolo¹

2017

JCT

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The availability of a minimally invasive patient simple, capable of providing tumor information, represents a valuable clinical tool. The liquid biopsy has the potential to achieve this need. Circulating cell free DNA (ccfDNA), other circulating nucleic acids such as microRNA and circulating tumor cells (CTCs), can be obtained from a peripheral blood sample. Liquid biopsy has been particularly studied in solid tumors, specially of the epitelial origin, such as a pancreatic carcinoma and advanced breast cancer. It has been considerably less applied to the study of non-solid tumors. It represents an important source for diagnosis, prognosis and predictive information. Also it is suitable to evaluate response to therapy and drugs pharmacokinetics. It provides a unique opportunity to evaluate the disease evolution in serial blood samples collection, otherwise difficult to obtain. Liquid biopsy can be rehearsed using different circulating biological fluids such as whole blood, serum, plasma and lymph, as well as, non-circulating fluids such as urine, feces, saliva, bile and accumulated pathological fluids such as ascites. This review summarizes the current status of circulating material analysis in non-solid tunors. It is specially focused on Hodgkin Lymphoma and among Non-Hodgkin Lymphoma, it refers particularly to Diffuse Large B cell Lymphoma, the most common aggressive Non-Hodgkin Lymphoma derived from germinal center B-cells in adults. It further discusses the benefit of liquid biopsy in oncohemtaological diseases and potential clinical applications.

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Somatic mutations of cell-free circulating DNA detected by next-generation sequencing reflect the genetic changes in both germinal center B-cell-like and activated B-cell-like diffuse large B-cell lymphomas at the time of diagnosis

Cited by 70 publications

References 14 publications

Next-Generation Sequencing in Diffuse Large B-Cell Lymphoma Highlights Molecular Divergence and Therapeutic Opportunities: a LYSA Study

Next-Generation Sequencing in Diffuse Large B-Cell Lymphoma Highlights Molecular Divergence and Therapeutic Opportunities: a LYSA Study

Dynamic monitoring of circulating tumor DNA in non-Hodgkin lymphoma

Liquid Biopsy in Liquid Tumors

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