Ultra-low-input cell-free DNA sequencing for tumor detection and characterization in a real-world pediatric brain tumor cohort
Molecular profiling of pediatric central nervous system (CNS) tumors has important clinical utility for guiding diagnostic and therapeutic strategies. Cell-free DNA (cfDNA) from liquid biopsies has been used for minimally invasive tumor profiling and longitudinal disease assessment in adult oncology...
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| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
28 June 2025
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| In: |
Acta Neuropathologica Communications
Year: 2025, Jahrgang: 13, Pages: 1-19 |
| ISSN: | 2051-5960 |
| DOI: | 10.1186/s40478-025-02024-w |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.1186/s40478-025-02024-w
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| Verfasserangaben: | Tom T. Fischer, Kendra K. Maaß, Pitithat Puranachot, Markus Mieskolainen, Martin Sill, Paulina S. Schad, Stefanie Volz, Fabian Rosing, Tatjana Wedig, Nathalie Schwarz, Agnes M.E. Finster, Florian Iser, Jochen Meyer, Felix Sahm, Olli Lohi, Ahmed El Damaty, Benedikt Brors, Hannu Haapasalo, Stefan M. Pfister, Joonas Haapasalo, Kristian W. Pajtler and Kristiina Nordfors |
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| 245 | 1 | 0 | |a Ultra-low-input cell-free DNA sequencing for tumor detection and characterization in a real-world pediatric brain tumor cohort |c Tom T. Fischer, Kendra K. Maaß, Pitithat Puranachot, Markus Mieskolainen, Martin Sill, Paulina S. Schad, Stefanie Volz, Fabian Rosing, Tatjana Wedig, Nathalie Schwarz, Agnes M.E. Finster, Florian Iser, Jochen Meyer, Felix Sahm, Olli Lohi, Ahmed El Damaty, Benedikt Brors, Hannu Haapasalo, Stefan M. Pfister, Joonas Haapasalo, Kristian W. Pajtler and Kristiina Nordfors |
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| 520 | |a Molecular profiling of pediatric central nervous system (CNS) tumors has important clinical utility for guiding diagnostic and therapeutic strategies. Cell-free DNA (cfDNA) from liquid biopsies has been used for minimally invasive tumor profiling and longitudinal disease assessment in adult oncology and pediatric hematology. However, in pediatric neuro-oncology, low cfDNA yields pose a major barrier to translating these assays from bench to bedside. Here, we implemented a low-coverage whole genome sequencing (lcWGS) assay for picogram-level cfDNA inputs and applied it to liquid biopsies from a sizeable, population-based, cross-entity pediatric CNS tumor cohort (n = 56 patients). Applying this protocol, cfDNA whole genome profiles were successfully acquired from all liquid biopsy samples (n = 61/61 serum, n = 56/56 CSF, 100%). Based on copy number variations (CNVs), circulating-tumor DNA (ctDNA) was detected in 2/61 serum (3%) and in 25/56 CSF (45%) samples across various brain tumor entities. The integration of cfDNA results with clinical data demonstrated the utility of CSF lcWGS as a biomarker assay at diagnosis to distinguish cancerous from non-cancerous pineal region lesions (n = 6 patients). Additionally, serial CSF assessment in n = 9 patients (n = 29 CSF samples) enabled minimally invasive disease monitoring, with the added value of molecular profile availability in n = 4/6 (67%) patients at relapse. Proof-of-concept data show the feasibility of serial CSF lcWGS to reveal tumor evolution, tumor heterogeneity and potential therapeutic vulnerabilities in a case of medulloblastoma and germ cell tumor. Our study underscores the clinical utility of a robust lcWGS-based liquid biopsy assay optimized for low-input samples. We identify use-cases for implementing liquid biopsies in the clinical management of pediatric CNS tumor patients and provide a strong rationale for integration into future trials. | ||
| 650 | 4 | |a Cell-free DNA | |
| 650 | 4 | |a Cerebrospinal fluid liquid biopsies | |
| 650 | 4 | |a Circulating-tumor DNA | |
| 650 | 4 | |a Copy number variation profiling | |
| 650 | 4 | |a Longitudinal molecular biomarkers | |
| 650 | 4 | |a Low-coverage whole genome sequencing | |
| 650 | 4 | |a Low-input samples | |
| 650 | 4 | |a Minimally-invasive disease monitoring | |
| 650 | 4 | |a Pediatric neuro-oncology | |
| 650 | 4 | |a Tumor evolution | |
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