Diagnosis of pediatric central nervous system tumors using methylation profiling of cfDNA from cerebrospinal fluid.
Humans
DNA Methylation
/ genetics
Child
Male
Female
Child, Preschool
Liquid Biopsy
/ methods
Circulating Tumor DNA
/ cerebrospinal fluid
Cell-Free Nucleic Acids
/ cerebrospinal fluid
Central Nervous System Neoplasms
/ genetics
Adolescent
Infant
Biomarkers, Tumor
/ cerebrospinal fluid
Brain Neoplasms
/ genetics
Proof of Concept Study
Central nervous system tumor
Cerebrospinal fluid
DNA methylation
Liquid biopsy
Pediatric oncology
Precision medicine
Journal
Clinical epigenetics
ISSN: 1868-7083
Titre abrégé: Clin Epigenetics
Pays: Germany
ID NLM: 101516977
Informations de publication
Date de publication:
05 Jul 2024
05 Jul 2024
Historique:
received:
04
04
2024
accepted:
17
06
2024
medline:
6
7
2024
pubmed:
6
7
2024
entrez:
5
7
2024
Statut:
epublish
Résumé
Pediatric central nervous system tumors remain challenging to diagnose. Imaging approaches do not provide sufficient detail to discriminate between different tumor types, while the histopathological examination of tumor tissue shows high inter-observer variability. Recent studies have demonstrated the accurate classification of central nervous system tumors based on the DNA methylation profile of a tumor biopsy. However, a brain biopsy holds significant risk of bleeding and damaging the surrounding tissues. Liquid biopsy approaches analyzing circulating tumor DNA show high potential as an alternative and less invasive tool to study the DNA methylation pattern of tumors. Here, we explore the potential of classifying pediatric brain tumors based on methylation profiling of the circulating cell-free DNA (cfDNA) in cerebrospinal fluid (CSF). For this proof-of-concept study, we collected cerebrospinal fluid samples from 19 pediatric brain cancer patients via a ventricular drain placed for reasons of increased intracranial pressure. Analyses on the cfDNA showed high variability of cfDNA quantities across patients ranging from levels below the limit of quantification to 40 ng cfDNA per milliliter of CSF. Classification based on methylation profiling of cfDNA from CSF was correct for 7 out of 20 samples in our cohort. Accurate results were mostly observed in samples of high quality, more specifically those with limited high molecular weight DNA contamination. Interestingly, we show that centrifugation of the CSF prior to processing increases the fraction of fragmented cfDNA to high molecular weight DNA. In addition, classification was mostly correct for samples with high tumoral cfDNA fraction as estimated by computational deconvolution (> 40%). In summary, analysis of cfDNA in the CSF shows potential as a tool for diagnosing pediatric nervous system tumors especially in patients with high levels of tumoral cfDNA in the CSF. Further optimization of the collection procedure, experimental workflow and bioinformatic approach is required to also allow classification for patients with low tumoral fractions in the CSF.
Identifiants
pubmed: 38970137
doi: 10.1186/s13148-024-01696-w
pii: 10.1186/s13148-024-01696-w
doi:
Substances chimiques
Circulating Tumor DNA
0
Cell-Free Nucleic Acids
0
Biomarkers, Tumor
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
87Subventions
Organisme : Fonds Wetenschappelijk Onderzoek
ID : 1S45323N
Organisme : Kom op tegen Kanker
ID : STI.VLK.2019.0009.01
Informations de copyright
© 2024. The Author(s).
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