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| Item Type: | Article |
|---|---|
| Title: | Circulating cell-free DNA assessment in biofluids from children with neuroblastoma demonstrates feasibility and potential for minimally invasive molecular diagnostics |
| Creators Name: | Lodrini, M. and Wünschel, J. and Thole-Kliesch, T.M. and Grimaldi, M. and Sprüssel, A. and Linke, R.B. and Hollander, J.F. and Tiburtius, D. and Künkele, A. and Schulte, J.H. and Lankes, E. and Elgeti, T. and Hundsdörfer, P. and Astrahantseff, K. and Simon, T. and Eggert, A. and Deubzer, H.E. |
| Abstract: | 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. |
| Keywords: | Liquid Biopsy, Cancer, Detection of Therapeutic Targets, Minimal Residual Disease, Precision Medicine, Real-Time Monitoring of Therapeutic Efficacy, ALK Mutation, ALK-Inhibitor, MYCN Amplification |
| Source: | Cancers |
| ISSN: | 2072-6694 |
| Publisher: | MDPI |
| Volume: | 14 |
| Number: | 9 |
| Page Range: | 2080 |
| Date: | 21 April 2022 |
| Official Publication: | https://doi.org/10.3390/cancers14092080 |
| PubMed: | View item in PubMed |
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