Serial assessment of measurable residual disease in medulloblastoma liquid biopsies.

Autor:	Liu APY; Division of Neuro-Oncology, Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Division of Brain Tumor Research, Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Smith KS; Division of Brain Tumor Research, Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Kumar R; Division of Brain Tumor Research, Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; St. Jude Graduate School of Biomedical Sciences, Memphis, TN 38105, USA., Paul L; Division of Brain Tumor Research, Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Bihannic L; Division of Brain Tumor Research, Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Lin T; Department of Biostatistics, St Jude Children's Research Hospital, Memphis, TN 38105, USA., Maass KK; Division of Pediatric Neuro-oncology, German Cancer Research Center, 69120 Heidelberg, Germany., Pajtler KW; Division of Pediatric Neuro-oncology, German Cancer Research Center, 69120 Heidelberg, Germany; Department of Pediatric Oncology, Hematology and Immunology, University Hospital of Heidelberg, 69120 Heidelberg, Germany., Chintagumpala M; Department of Pediatrics, Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA., Su JM; Department of Pediatrics, Texas Children's Cancer Center, Baylor College of Medicine, Houston, TX 77030, USA., Bouffet E; Division of Hematology-Oncology, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada., Fisher MJ; Division of Oncology, Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA., Gururangan S; Preston A. Wells Jr. Center for Brain Tumor Therapy, UF Health Shands Hospital, Gainesville, FL 32608, USA., Cohn R; Kids Cancer Centre, Sydney Children's Hospital, Randwick, and UNSW, Sydney, NSW 2031, Australia., Hassall T; Queensland Children's Hospital, Brisbane, QLD 4101, Australia., Hansford JR; Children's Cancer Centre, The Royal Children's Hospital, Murdoch Children's Research Institute, Department of Pediatrics, University of Melbourne, Melbourne, VIC 3052, Australia., Klimo P Jr; Department of Surgery, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Department of Neurosurgery, University of Tennessee Health Science Center, Memphis, TN 38105, USA; Le Bonheur Neuroscience Institute, Le Bonheur Children's Hospital, Memphis, TN 38105, USA., Boop FA; Department of Surgery, St. Jude Children's Research Hospital, Memphis, TN 38105, USA; Department of Neurosurgery, University of Tennessee Health Science Center, Memphis, TN 38105, USA; Le Bonheur Neuroscience Institute, Le Bonheur Children's Hospital, Memphis, TN 38105, USA., Stewart CF; Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Harreld JH; Department of Radiology, Dartmouth Geisel School of Medicine, Hanover, NH 03755, USA., Merchant TE; Department of Radiation Oncology, St Jude Children's Research Hospital, Memphis, TN 38105, USA., Tatevossian RG; Diagnostic Biomarkers Shared Resource, Department of Pathology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Neale G; Hartwell Center, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Lear M; Department of Pathology, St Jude Children's Research Hospital, Memphis, TN 38105, USA., Klco JM; Department of Pathology, St Jude Children's Research Hospital, Memphis, TN 38105, USA., Orr BA; Department of Pathology, St Jude Children's Research Hospital, Memphis, TN 38105, USA., Ellison DW; Department of Pathology, St Jude Children's Research Hospital, Memphis, TN 38105, USA., Gilbertson RJ; Cancer Research UK Cambridge Centre, CRUK Cambridge Institute, Li Ka Shing Centre, Cambridge CB2 0RE, UK., Onar-Thomas A; Department of Biostatistics, St Jude Children's Research Hospital, Memphis, TN 38105, USA., Gajjar A; Division of Neuro-Oncology, Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Robinson GW; Division of Neuro-Oncology, Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA., Northcott PA; Division of Brain Tumor Research, Department of Developmental Neurobiology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA. Electronic address: paul.northcott@stjude.org.
Jazyk:	angličtina
Zdroj:	Cancer cell [Cancer Cell] 2021 Nov 08; Vol. 39 (11), pp. 1519-1530.e4. Date of Electronic Publication: 2021 Oct 21.
DOI:	10.1016/j.ccell.2021.09.012
Abstrakt:	Nearly one-third of children with medulloblastoma, a malignant embryonal tumor of the cerebellum, succumb to their disease. Conventional response monitoring by imaging and cerebrospinal fluid (CSF) cytology remains challenging, and a marker for measurable residual disease (MRD) is lacking. Here, we show the clinical utility of CSF-derived cell-free DNA (cfDNA) as a biomarker of MRD in serial samples collected from children with medulloblastoma (123 patients, 476 samples) enrolled on a prospective trial. Using low-coverage whole-genome sequencing, tumor-associated copy-number variations in CSF-derived cfDNA are investigated as an MRD surrogate. MRD is detected at baseline in 85% and 54% of patients with metastatic and localized disease, respectively. The number of MRD-positive patients declines with therapy, yet those with persistent MRD have significantly higher risk of progression. Importantly, MRD detection precedes radiographic progression in half who relapse. Our findings advocate for the prospective assessment of CSF-derived liquid biopsies in future trials for medulloblastoma. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2021. Published by Elsevier Inc.)
Databáze:	MEDLINE
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