TY - JOUR
T1 - Reliable tumor detection by whole-genome methylation sequencing of cell-free DNA in cerebrospinal fluid of pediatric medulloblastoma
AU - Li, Jia
AU - Zhao, Sibo
AU - Lee, Minjung
AU - Yin, Yue
AU - Li, Jin
AU - Zhou, Yubin
AU - Ballester, Leomar Y.
AU - Esquenazi, Yoshua
AU - Dashwood, Roderick H.
AU - Davies, Peter J.A.
AU - Williams Parsons, D.
AU - Li, Xiao Nan
AU - Huang, Yun
AU - Sun, Deqiang
N1 - Publisher Copyright:
Copyright © 2020 The Authors, some rights reserved;
PY - 2020/10
Y1 - 2020/10
N2 - Medulloblastoma (MB), the most common form of pediatric brain malignancy, has a low frequency of oncogenic mutations but pronouncedly abnormal DNA methylation changes. Epigenetic analysis of circulating cell-free tumor DNA (ctDNA) by liquid biopsy offers an approach for real-time monitoring of tumor status without tumor dissection. In this study, we identified 6598 differentially methylated CpGs in both MB tumors and the ctDNA isolated from matched cerebrospinal fluid (CSF) compared with normal cerebellum, which could be used to detect MB tumor occurrence and determine its subtype. Furthermore, DNA methylation changes in serial CSF samples could be used to monitor the treatment response and tumor recurrence. Integrating our data with large public datasets, we identified reliable MB DNA methylation signatures in ctDNA that have potential diagnostic and prognostic values. Our study sets the stage for exploiting epigenetic markers in CSF to improve the clinical management of patients with MB.
AB - Medulloblastoma (MB), the most common form of pediatric brain malignancy, has a low frequency of oncogenic mutations but pronouncedly abnormal DNA methylation changes. Epigenetic analysis of circulating cell-free tumor DNA (ctDNA) by liquid biopsy offers an approach for real-time monitoring of tumor status without tumor dissection. In this study, we identified 6598 differentially methylated CpGs in both MB tumors and the ctDNA isolated from matched cerebrospinal fluid (CSF) compared with normal cerebellum, which could be used to detect MB tumor occurrence and determine its subtype. Furthermore, DNA methylation changes in serial CSF samples could be used to monitor the treatment response and tumor recurrence. Integrating our data with large public datasets, we identified reliable MB DNA methylation signatures in ctDNA that have potential diagnostic and prognostic values. Our study sets the stage for exploiting epigenetic markers in CSF to improve the clinical management of patients with MB.
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U2 - 10.1126/sciadv.abb5427
DO - 10.1126/sciadv.abb5427
M3 - Article
C2 - 33067228
AN - SCOPUS:85093705457
SN - 2375-2548
VL - 6
JO - Science Advances
JF - Science Advances
IS - 42
M1 - eabb5427
ER -