Next-generation sequencing of cerebrospinal fluid for clinical molecular diagnostics in pediatric, adolescent and young adult brain tumor patients.

Autor:	Miller AM; Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Szalontay L; Department of Pediatrics, Columbia University Irving Medical Center, New York, New York, USA., Bouvier N; Pediatric Translational Medicine Program, Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Hill K; Pediatric Translational Medicine Program, Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Ahmad H; Pediatric Translational Medicine Program, Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Rafailov J; Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Lee AJ; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Rodriguez-Sanchez MI; Pediatric Translational Medicine Program, Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Yildirim O; Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Patel A; Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Bale TA; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Benhamida JK; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Benayed R; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Arcila ME; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Donzelli M; Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Dunkel IJ; Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Gilheeney SW; Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Khakoo Y; Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Kramer K; Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Sait SF; Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Greenfield JP; Department of Pediatrics, Weill Cornell Medical College, New York, New York, USA.; Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA.; Department of Neurological Surgery, Weill Cornell Medical College, New York, New York, USA.; Department of Neurological Surgery, Columbia University Irving Medical Center, New York, New York, USA., Souweidane MM; Department of Pediatrics, Weill Cornell Medical College, New York, New York, USA.; Department of Neurosurgery, Memorial Sloan Kettering Cancer Center, New York, New York, USA.; Department of Neurological Surgery, Weill Cornell Medical College, New York, New York, USA.; Department of Neurological Surgery, Columbia University Irving Medical Center, New York, New York, USA., Haque S; Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Mauguen A; Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Berger MF; Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, USA.; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Mellinghoff IK; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA.; Department of Pharmacology, Weill Cornell Medical College, New York, New York, USA., Karajannis MA; Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York, USA.; Department of Pediatrics, Weill Cornell Medical College, New York, New York, USA.
Jazyk:	angličtina
Zdroj:	Neuro-oncology [Neuro Oncol] 2022 Oct 03; Vol. 24 (10), pp. 1763-1772.
DOI:	10.1093/neuonc/noac035
Abstrakt:	Background: Safe sampling of central nervous system tumor tissue for diagnostic purposes may be difficult if not impossible, especially in pediatric patients, and an unmet need exists to develop less invasive diagnostic tests. Methods: We report our clinical experience with minimally invasive molecular diagnostics using a clinically validated assay for sequencing of cerebrospinal fluid (CSF) cell-free DNA (cfDNA). All CSF samples were collected as part of clinical care, and results reported to both clinicians and patients/families. Results: We analyzed 64 CSF samples from 45 pediatric, adolescent and young adult (AYA) patients (pediatric = 25; AYA = 20) with primary and recurrent brain tumors across 12 histopathological subtypes including high-grade glioma (n = 10), medulloblastoma (n = 10), pineoblastoma (n = 5), low-grade glioma (n = 4), diffuse leptomeningeal glioneuronal tumor (DLGNT) (n = 4), retinoblastoma (n = 4), ependymoma (n = 3), and other (n = 5). Somatic alterations were detected in 30/64 samples (46.9%) and in at least one sample per unique patient in 21/45 patients (46.6%). CSF cfDNA positivity was strongly associated with the presence of disseminated disease at the time of collection (81.5% of samples from patients with disseminated disease were positive). No association was seen between CSF cfDNA positivity and the timing of CSF collection during the patient's disease course. Conclusions: We identified three general categories where CSF cfDNA testing provided additional relevant diagnostic, prognostic, and/or therapeutic information, impacting clinical assessment and decision making: (1) diagnosis and/or identification of actionable alterations; (2) monitor response to therapy; and (3) tracking tumor evolution. Our findings support broader implementation of clinical CSF cfDNA testing in this population to improve care. (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
Databáze:	MEDLINE
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