Serial assessment of measurable residual disease in medulloblastoma liquid biopsies

Anthony P Y Liu, Kyle S Smith, Rahul Kumar, Leena Paul, Laure Bihannic, Tong Lin, Kendra K Maass, Kristian W Pajtler, Murali Chintagumpala, Jack M Su, Eric Bouffet, Michael J Fisher, Sridharan Gururangan, Richard Cohn, Tim Hassall, Jordan R Hansford, Paul Klimo, Frederick A Boop, Clinton F Stewart, Julie H HarreldThomas E Merchant, Ruth G Tatevossian, Geoffrey Neale, Matthew Lear, Jeffery M Klco, Brent A Orr, David W Ellison, Richard J Gilbertson, Arzu Onar-Thomas, Amar Gajjar, Giles W Robinson, Paul A Northcott

Research output: Contribution to journalArticlepeer-review

52 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)1519-1530.e4
JournalCancer Cell
Issue number11
Publication statusPublished or Issued - 8 Nov 2021
Externally publishedYes


  • Biomarkers, Tumor/cerebrospinal fluid
  • Cell-Free Nucleic Acids/cerebrospinal fluid
  • Cerebellar Neoplasms/cerebrospinal fluid
  • Child
  • Chromosomal Instability
  • DNA Copy Number Variations
  • Disease Progression
  • Female
  • Humans
  • Liquid Biopsy
  • Male
  • Medulloblastoma/cerebrospinal fluid
  • Neoplasm, Residual
  • Prospective Studies
  • Whole Genome Sequencing/methods

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