Cerebrospinal fluid liquid biopsy by low-pass whole genome sequencing for clinical disease monitoring in pediatric embryonal tumors.

Autor:	Crotty EE; Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.; Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, Washington, USA.; Division of Hematology, Oncology, Bone Marrow Transplant & Cellular Therapy, Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, Washington, USA., Paulson VA; Genetics and Solid Tumors Laboratory, Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, Washington, USA.; Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, Washington, USA., Ronsley R; Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.; Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, Washington, USA.; Division of Hematology, Oncology, Bone Marrow Transplant & Cellular Therapy, Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, Washington, USA., Vitanza NA; Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.; Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, Washington, USA.; Division of Hematology, Oncology, Bone Marrow Transplant & Cellular Therapy, Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, Washington, USA., Lee A; Division of Neurosurgery, Department of Neurological Surgery, Seattle Children's Hospital, University of Washington, Seattle, Washington, USA., Hauptman J; Division of Neurosurgery, Department of Neurological Surgery, Seattle Children's Hospital, University of Washington, Seattle, Washington, USA., Goldstein HE; Division of Neurosurgery, Department of Neurological Surgery, Seattle Children's Hospital, University of Washington, Seattle, Washington, USA., Lockwood CM; Genetics and Solid Tumors Laboratory, Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, Washington, USA.; Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, Washington, USA., Leary SES; Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.; Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, Washington, USA.; Division of Hematology, Oncology, Bone Marrow Transplant & Cellular Therapy, Department of Pediatrics, Seattle Children's Hospital, University of Washington, Seattle, Washington, USA., Cole BL; Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, Washington, USA.; Ben Towne Center for Childhood Cancer Research, Seattle Children's Research Institute, Seattle, Washington, USA.
Jazyk:	angličtina
Zdroj:	Neuro-oncology advances [Neurooncol Adv] 2024 Jul 25; Vol. 6 (1), pp. vdae126. Date of Electronic Publication: 2024 Jul 25 (Print Publication: 2024).
DOI:	10.1093/noajnl/vdae126
Abstrakt:	Background: Liquid biopsy assays that detect cell-free DNA (cfDNA) in cerebrospinal fluid (CSF) are a promising tool for disease monitoring in pediatric patients with primary central nervous system (CNS) tumors. As a compliment to tissue-derived molecular analyses, CSF liquid biopsy has the potential to transform risk stratification, prognostication, and precision medicine approaches. Methods: In this pilot study, we evaluated a clinical pipeline to determine feasibility and sensitivity of low-pass whole genome sequencing (LP-WGS) of CSF-derived cfDNA from patients with CNS embryonal tumors. Thirty-two longitudinal CSF samples collected from 17 patients with molecularly characterized medulloblastoma (12), embryonal tumor with multilayered rosettes (2), CNS embryonal tumor, not elsewhere classified (NEC) (2), and atypical teratoid/rhabdoid tumor (1) were analyzed. Results: Adequate CSF-derived cfDNA for LP-WGS analysis was obtained in 94% of samples (30/32). Copy number variants compatible with neoplasia were detected in 90% (27/30) and included key alterations, such as isodicentric ch17, monosomy 6, and MYCN amplification, among others. Compared to tissue specimens, LP-WGS detected additional aberrations in CSF not previously identified in corresponding primary tumor specimens, suggesting a more comprehensive profile of tumor heterogeneity or evolution of cfDNA profiles over time. Among the 12 CSF samples obtained at initial staging, only 2 (17%) were cytologically positive, compared to 11 (92%) that were copy number positive by LP-WGS. Conclusions: LP-WGS of CSF-derived cfDNA is feasible using a clinical platform, with greater sensitivity for tumor detection compared to conventional CSF cytologic analysis at initial staging. Large prospective studies are needed to further evaluate LP-WGS as a predictive biomarker. Competing Interests: None declared. (© The Author(s) 2024. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)
Databáze:	MEDLINE
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