In-depth cell-free DNA sequencing reveals genomic landscape of Hodgkin's lymphoma and facilitates ultrasensitive residual disease detection.

Autor:	Sobesky S; Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Köln, Germany; Cancer Center Cologne Essen - Partner Site Cologne, CIO Cologne, University of Cologne, Köln, Germany; German Hodgkin Study Group, Cologne, Germany., Mammadova L; Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Köln, Germany; Cancer Center Cologne Essen - Partner Site Cologne, CIO Cologne, University of Cologne, Köln, Germany; German Hodgkin Study Group, Cologne, Germany., Cirillo M; University of Western Australia and Royal Perth Hospital, Perth, Australia., Drees EEE; Amsterdam UMC, Vrije Universiteit Amsterdam, Exosomes Research Group, Department of Pathology, Cancer Center Amsterdam, Amsterdam, the Netherlands; Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Hematology, Cancer Center Amsterdam, Amsterdam, the Netherlands., Mattlener J; Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Köln, Germany; Cancer Center Cologne Essen - Partner Site Cologne, CIO Cologne, University of Cologne, Köln, Germany; German Hodgkin Study Group, Cologne, Germany., Dörr H; Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Köln, Germany; Cancer Center Cologne Essen - Partner Site Cologne, CIO Cologne, University of Cologne, Köln, Germany; German Hodgkin Study Group, Cologne, Germany., Altmüller J; Cologne Center for Genomics (CCG), University of Cologne, Cologne, Germany., Shi Z; Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Köln, Germany; Cancer Center Cologne Essen - Partner Site Cologne, CIO Cologne, University of Cologne, Köln, Germany., Bröckelmann PJ; Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Köln, Germany; Cancer Center Cologne Essen - Partner Site Cologne, CIO Cologne, University of Cologne, Köln, Germany; German Hodgkin Study Group, Cologne, Germany., Weiss J; Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Köln, Germany; Cancer Center Cologne Essen - Partner Site Cologne, CIO Cologne, University of Cologne, Köln, Germany., Kreissl S; Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Köln, Germany; Cancer Center Cologne Essen - Partner Site Cologne, CIO Cologne, University of Cologne, Köln, Germany; German Hodgkin Study Group, Cologne, Germany., Sasse S; Department IV of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, RWTH Aachen University, Aachen, Germany., Ullrich RT; Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Köln, Germany; Cancer Center Cologne Essen - Partner Site Cologne, CIO Cologne, University of Cologne, Köln, Germany., Reinke S; University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany., Klapper W; University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany., Gerhard-Hartmann E; Department of Pathology, University of Würzburg, Würzburg, Germany; Comprehensive Cancer Center Mainfranken, Würzburg, Germany., Rosenwald A; Department of Pathology, University of Würzburg, Würzburg, Germany; Comprehensive Cancer Center Mainfranken, Würzburg, Germany., Roemer MGM; Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Hematology, Cancer Center Amsterdam, Amsterdam, the Netherlands., Nürnberg P; Cologne Center for Genomics (CCG), University of Cologne, Cologne, Germany., Hagenbeek A; Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Hematology, Cancer Center Amsterdam, Amsterdam, the Netherlands., Zijlstra JM; Amsterdam UMC, Vrije Universiteit Amsterdam, Department of Hematology, Cancer Center Amsterdam, Amsterdam, the Netherlands., Pegtel DM; Amsterdam UMC, Vrije Universiteit Amsterdam, Exosomes Research Group, Department of Pathology, Cancer Center Amsterdam, Amsterdam, the Netherlands., Engert A; Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Köln, Germany; Cancer Center Cologne Essen - Partner Site Cologne, CIO Cologne, University of Cologne, Köln, Germany; German Hodgkin Study Group, Cologne, Germany., Borchmann P; Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Köln, Germany; Cancer Center Cologne Essen - Partner Site Cologne, CIO Cologne, University of Cologne, Köln, Germany; German Hodgkin Study Group, Cologne, Germany., von Tresckow B; German Hodgkin Study Group, Cologne, Germany; Department of Hematology and Stem Cell Transplantation, University Hospital Essen, University Duisburg-Essen, German Cancer Consortium (DKTK partner site Essen), Essen, Germany; Cancer Center Cologne Essen - Partner Site Essen, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, Duisburg, Germany., Borchmann S; Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, University of Cologne, Köln, Germany; Cancer Center Cologne Essen - Partner Site Cologne, CIO Cologne, University of Cologne, Köln, Germany; German Hodgkin Study Group, Cologne, Germany. Electronic address: sven.borchmann@uk-koeln.de.
Jazyk:	angličtina
Zdroj:	Med (New York, N.Y.) [Med (N Y)] 2021 Oct 08; Vol. 2 (10), pp. 1171-1193.e11.
DOI:	10.1016/j.medj.2021.09.002
Abstrakt:	Background: Individualization of treatment in Hodgkin's lymphoma is necessary to improve cure rates and reduce treatment side effects. Currently, it is hindered by a lack of genomic characterization and sensitive molecular response assessment. Sequencing of cell-free DNA is a powerful strategy to understand the cancer genome and can be used for extremely sensitive disease monitoring. In Hodgkin's lymphoma, a high proportion of cell-free DNA is tumor-derived, whereas traditional tumor biopsies only contain a little tumor-derived DNA. Methods: We comprehensively genotype and assess minimal residual disease in 121 patients with baseline plasma as well as 77 follow-up samples from a subset of patients with our targeted cell-free DNA sequencing platform. Findings: We present an integrated landscape of mutations and copy number variations in Hodgkin's lymphoma. In addition, we perform a deep analysis of mutational processes driving Hodgkin's lymphoma, investigate the clonal structure of Hodgkin's lymphoma, and link several genotypes to Hodgkin's lymphoma phenotypes and outcome. Finally, we show that minimal residual disease assessment by repeat cell-free DNA sequencing, as early as a week after treatment initiation, predicts treatment response and progression-free survival, allowing highly improved treatment guidance and relapse prediction. Conclusions: Our targeted cell-free DNA sequencing platform reveals the genomic landscape of Hodgkin's lymphoma and facilitates ultrasensitive detection of minimal residual disease. Funding: Mildred Scheel School of Oncology Aachen-Bonn-Cologne-Düsseldorf MD Research Stipend, Next Generation Sequencing Competence Network grant 423957469, Deutsche Krebshilfe grant 70112502, Deutsche Forschungsgemeinschaft (DFG) grant EN 179/13-1, the HL MRD consortium, and the Frau-Weiskam und Christel Ruranski-Stiftung. Competing Interests: Declaration of Interests P.J.B. reports research grants from BeiGene, Bristol Myers Squibb, Merck Sharpe & Dohme, and Takeda and personal fees and non-financial support from Bristol-Myers Squibb, Celgene, and Takeda, all outside the submitted work. S.S. received travel grants from GSK. D.M.P. reports being founder and CSO of Exbiome and an occasional advisor for Takeda. B.v.T. reports personal fees and nonfinancial support from Bristol-Myers Squibb; personal fees from Amgen, Pfizer, Gilead Sciences, Pentixapharm, and Roche; grants, personal fees, and nonfinancial support from MSD and Takeda; and grants, personal fees, and nonfinancial support from Novartis. S.B. reports being founder, CEO, and shareholder of Liqomics and personal fees and non-financial support from Bristol-Myers Squibb and Takeda outside the submitted work. (Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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