Lodrini, Marco 
ORCID: 0000-0003-4434-529X, Wuenschel, Jasmin, Thole-Kliesch, Theresa M., Grimaldi, Maddalena, Sprussel, Annika, Linke, Rasmus B., Hollander, Jan F., Tiburtius, Daniela, Kunkele, Annette ORCID: 0000-0002-8406-5412, Schulte, Johannes H., Lankes, Erwin, Elgeti, Thomas, Hundsdorfer, Patrick, Astrahantseff, Kathy, Simon, Thorsten ORCID: 0000-0002-3425-8451, Eggert, Angelika ORCID: 0000-0003-3476-8184 and Deubzer, Hedwig E.
(2022).
Circulating Cell-Free DNA Assessment in Biofluids from Children with Neuroblastoma Demonstrates Feasibility and Potential for Minimally Invasive Molecular Diagnostics.
Cancers, 14 (9).
BASEL:
MDPI.
ISSN 2072-6694
Abstract
Simple Summary The invasive nature of surgical biopsies prevents their sequential application to monitor disease. Single biopsies fail to reflect cancer dynamics, intratumor heterogeneity, and drug sensitivities that change over time. Detection and characterization of cell-free circulating tumor DNA in biofluids from patients with solid tumors may better support disease monitoring and provide advanced molecular information for clinical decision-making toward personalized medicine. Here, we investigated the cell-free DNA characteristics in blood, bone marrow, cerebrospinal fluid, and urine provided from 84 infants and children with low-, intermediate-, or high-risk neuroblastoma. We report characteristic size distribution and concentration patterns for each biofluid to provide information to support the development of successful liquid biopsy biobanking strategies. We investigate potential correlations between disease activity and cfDNA concentration and provide strong evidence that markers specific for neuroblastoma can be detected in very small blood volumes from infants. 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.
| Item Type: | Journal Article | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| URN: | urn:nbn:de:hbz:38-687312 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DOI: | 10.3390/cancers14092080 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Journal or Publication Title: | Cancers | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Volume: | 14 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Number: | 9 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Date: | 2022 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Publisher: | MDPI | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Place of Publication: | BASEL | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| ISSN: | 2072-6694 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Language: | English | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Faculty: | Unspecified | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Divisions: | Unspecified | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Subjects: | no entry | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| URI: | http://kups.ub.uni-koeln.de/id/eprint/68731 |
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