Circulating Cell-Free DNA Assessment in Biofluids from Children with Neuroblastoma Demonstrates Feasibility and Potential for Minimally Invasive Molecular Diagnostics.

Autor: Lodrini M; Department of Pediatric Hematology and Oncology, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany.; Experimental and Clinical Research Center (ECRC) of the Charité and the Max-Delbrück-Center for Molecular Medicine (MDC) in the Helmholtz Association, 13125 Berlin, Germany.; Max-Delbrück-Center for Molecular Medicine (MDC) in the Helmholtz Association, 13125 Berlin, Germany.; German Cancer Consortium (DKTK), Partner Site Berlin, 10117 Berlin, Germany.; German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany., Wünschel J; Department of Pediatric Hematology and Oncology, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany.; Experimental and Clinical Research Center (ECRC) of the Charité and the Max-Delbrück-Center for Molecular Medicine (MDC) in the Helmholtz Association, 13125 Berlin, Germany.; Max-Delbrück-Center for Molecular Medicine (MDC) in the Helmholtz Association, 13125 Berlin, Germany., Thole-Kliesch TM; Department of Pediatric Hematology and Oncology, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany., Grimaldi M; Department of Pediatric Hematology and Oncology, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany.; Experimental and Clinical Research Center (ECRC) of the Charité and the Max-Delbrück-Center for Molecular Medicine (MDC) in the Helmholtz Association, 13125 Berlin, Germany.; Max-Delbrück-Center for Molecular Medicine (MDC) in the Helmholtz Association, 13125 Berlin, Germany., Sprüssel A; Department of Pediatric Hematology and Oncology, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany., Linke RB; Department of Pediatric Hematology and Oncology, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany., Hollander JF; Department of Pediatric Hematology and Oncology, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany., Tiburtius D; Department of Pediatric Hematology and Oncology, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany.; German Cancer Consortium (DKTK), Partner Site Berlin, 10117 Berlin, Germany.; German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany., Künkele A; Department of Pediatric Hematology and Oncology, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany.; German Cancer Consortium (DKTK), Partner Site Berlin, 10117 Berlin, Germany.; German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.; Berlin Institute of Health at Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany., Schulte JH; Department of Pediatric Hematology and Oncology, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany.; German Cancer Consortium (DKTK), Partner Site Berlin, 10117 Berlin, Germany.; German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany., Lankes E; Department of Pediatric Endocrinology and Diabetes, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany.; Center for Chronically Sick Children, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany., Elgeti T; Department of Radiology (Including Pediatric Radiology), Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany., Hundsdörfer P; Department of Pediatric Hematology and Oncology, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany.; Department of Pediatric Oncology, Helios Klinikum Berlin Burch, 13125 Berlin, Germany., Astrahantseff K; Department of Pediatric Hematology and Oncology, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany., Simon T; Department of Pediatric Oncology and Hematology, Children's Hospital, University of Cologne, 50924 Cologne, Germany., Eggert A; Department of Pediatric Hematology and Oncology, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany.; German Cancer Consortium (DKTK), Partner Site Berlin, 10117 Berlin, Germany.; German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.; Berlin Institute of Health at Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany., Deubzer HE; Department of Pediatric Hematology and Oncology, Charité-Universitätsmedizin Berlin, 13353 Berlin, Germany.; Experimental and Clinical Research Center (ECRC) of the Charité and the Max-Delbrück-Center for Molecular Medicine (MDC) in the Helmholtz Association, 13125 Berlin, Germany.; Max-Delbrück-Center for Molecular Medicine (MDC) in the Helmholtz Association, 13125 Berlin, Germany.; German Cancer Consortium (DKTK), Partner Site Berlin, 10117 Berlin, Germany.; German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany.; Berlin Institute of Health at Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2022 Apr 21; Vol. 14 (9). Date of Electronic Publication: 2022 Apr 21.
DOI: 10.3390/cancers14092080
Abstrakt: Liquid biopsy strategies in pediatric patients are challenging due to low body weight. This study investigated cfDNA size distribution and concentration in blood, bone marrow, cerebrospinal fluid, and urine from 84 patients with neuroblastoma classified as low ( n = 28), intermediate ( n = 6), or high risk ( n = 50) to provide key data for liquid biopsy biobanking strategies. The average volume of blood and bone marrow plasma provided ranged between 1 and 2 mL. Analysis of 637 DNA electropherograms obtained by Agilent TapeStation measurement revealed five different major profiles and characteristic DNA size distribution patterns for each of the biofluids. The proportion of samples containing primarily cfDNA was, at 85.5%, the highest for blood plasma. The median cfDNA concentration amounted to 6.28 ng/mL (blood plasma), 58.2 ng/mL (bone marrow plasma), 0.08 ng/mL (cerebrospinal fluid), and 0.49 ng/mL (urine) in samples. Meta-analysis of the dataset demonstrated that multiple cfDNA-based assays employing the same biofluid sample optimally require sampling volumes of 1 mL for blood and bone marrow plasma, 2 mL for cerebrospinal fluid, and as large as possible for urine samples. A favorable response to treatment was associated with a rapid decrease in blood-based cfDNA concentration in patients with high-risk neuroblastoma. Blood-based cfDNA concentration was not sufficient as a single parameter to indicate high-risk disease recurrence. We provide proof of concept that monitoring neuroblastoma-specific markers in very small blood volumes from infants is feasible.
Databáze: MEDLINE
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