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16.05.2024 | Research

Detection of tumor-derived cell-free DNA in cerebrospinal fluid using a clinically validated targeted sequencing panel for pediatric brain tumors

verfasst von: Rebecca Ronsley, Kristine A. Karvonen, Bonnie Cole, Vera Paulson, Jeff Stevens, Erin E. Crotty, Jason Hauptman, Amy Lee, Shannon M. Stasi, Christina M. Lockwood, Sarah E. S. Leary

Erschienen in: Journal of Neuro-Oncology

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Abstract

Purpose

Clinical sequencing of tumor DNA is necessary to render an integrated diagnosis and select therapy for children with primary central nervous system (CNS) tumors, but neurosurgical biopsy is not without risk. In this study, we describe cell-free DNA (cfDNA) in blood and cerebrospinal fluid (CSF) as sources for “liquid biopsy” in pediatric brain tumors.

Methods

CSF samples were collected by lumbar puncture, ventriculostomy, or surgery from pediatric patients with CNS tumors. Following extraction, CSF-derived cfDNA was sequenced using UW-OncoPlex™, a clinically validated next-generation sequencing platform. CSF-derived cfDNA results and paired plasma and tumor samples concordance was also evaluated.

Results

Seventeen CSF samples were obtained from 15 pediatric patients with primary CNS tumors. Tumor types included medulloblastoma (n = 7), atypical teratoid/rhabdoid tumor (n = 2), diffuse midline glioma with H3 K27 alteration (n = 4), pilocytic astrocytoma (n = 1), and pleomorphic xanthoastrocytoma (n = 1). CSF-derived cfDNA was detected in 9/17 (53%) of samples, and sufficient for sequencing in 8/10 (80%) of extracted samples. All somatic mutations and copy-number variants were also detected in matched tumor tissue, and tumor-derived cfDNA was absent in plasma samples and controls. Tumor-derived cfDNA alterations were detected in the absence of cytological evidence of malignant cells in as little as 200 µl of CSF. Several clinically relevant alterations, including a KIAA1549::BRAF fusion were detected.

Conclusions

Clinically relevant genomic alterations are detectable using CSF-derived cfDNA across a range of pediatric brain tumors. Next-generation sequencing platforms are capable of producing a high yield of DNA alterations with 100% concordance rate with tissue analysis.

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Titel: Detection of tumor-derived cell-free DNA in cerebrospinal fluid using a clinically validated targeted sequencing panel for pediatric brain tumors
verfasst von: Rebecca Ronsley
Kristine A. Karvonen
Bonnie Cole
Vera Paulson
Jeff Stevens
Erin E. Crotty
Jason Hauptman
Amy Lee
Shannon M. Stasi
Christina M. Lockwood
Sarah E. S. Leary
Publikationsdatum: 16.05.2024
Verlag: Springer US
Erschienen in: Journal of Neuro-Oncology
Print ISSN: 0167-594X
Elektronische ISSN: 1573-7373
DOI: https://doi.org/10.1007/s11060-024-04645-y

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