Cell-free tumor DNA (ctDNA) from cerebrospinal fluid (CSF) of pediatric patients with medulloblastoma demonstrated a distinct methylation profile compared with controls, and the methylation pattern changed during treatment, according to the results of a study published in Science Advances.

Pediatric medulloblastoma typically harbors few gene mutations, but recent studies demonstrate that there are substantial abnormal DNA methylation changes compared with normal tissue. ctDNA analysis of CSF  is a promising approach to detect DNA methylation in pediatric medulloblastoma.

ctDNA was collected from the CSF of pediatric patients with medulloblastoma and matched controls and the genome-wide methylation pattern was evaluated by WGBS. The methylation pattern was then trained and validated using a publically-available dataset from pediatric patients with medulloblastoma.

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There were 6598 differentially methylated CpGs identified in the ctDNA from the CSF of both normal cerebellum and medulloblastoma tumors. There was a distinct pattern of DNA methylation among medulloblastoma tumors compared with normal tissue, which was similar in the ctDNA from the CSF.

Further analysis demonstrated that the ctDNA methylation pattern was distinct between medulloblastoma and nontumor CSF samples. The methylation pattern could also distinguish between the subtypes of medulloblastoma.

“These data strongly suggest that the signature CpGs and their DAN methylation in medulloblastoma CSF consistently reflect medulloblastoma tumor signatures and can be used as  a potential CSF biomarker to indicate the presence of medulloblastoma,” the authors wrote.

The ctDNA methylation pattern also changed during treatment, correlating with treatment response. Changes in methylation of a single CpG site was associated with overall survival, and may be used to categorize patients into low- and high-risk groups.

The authors concluded that “overall, DNA methylation and hydroxymethylation signatures in CSF ctDNA can serve as valuable epigenetic markers to guide the clinical management of patients with medulloblastoma.”


Li J, Zhao S, Lee M, et al. Reliable tumor detection by whole-genome methylation sequencing of cell-free DNA in cerebrospinal fluid of pediatric medulloblastoma. Sci Adv. 2020;6:eabb5427. doi:10.1126/sciadv.abb5427