Detection of cell-free DNA fragmentation and copy number alterations in cerebrospinal fluid from glioma patients

Research output: Contribution to journalArticle


  • Florent Mouliere
  • Richard Mair
  • Dineika Chandrananda
  • Francesco Marass
  • Christopher G. Smith
  • Jing Su
  • James Morris
  • Kevin M. Brindle
  • Nitzan Rosenfeld

Colleges, School and Institutes

External organisations

  • University of Cambridge


Glioma is difficult to detect or characterize using current liquid biopsy approaches. Detection of cell-free tumor DNA (cftDNA) in cerebrospinal fluid (CSF) has been proposed as an alternative to detection in plasma. We used shallow whole-genome sequencing (sWGS, at a coverage of < 0.4×) of cell-free DNA from the CSF of 13 patients with primary glioma to determine somatic copy number alterations and DNA fragmentation patterns. This allowed us to determine the presence of cftDNA in CSF without any prior knowledge of point mutations present in the tumor. We also showed that the fragmentation pattern of cell-free DNA in CSF is different from that in plasma. This low-cost screening method provides information on the tumor genome and can be used to target those patients with high levels of cftDNA for further larger-scale sequencing, such as by whole-exome and whole-genome sequencing.


Original languageEnglish
Article numbere9323
JournalEMBO Molecular Medicine
Early online date6 Nov 2018
Publication statusE-pub ahead of print - 6 Nov 2018


  • cell-free DNA, cerebrospinal fluid, fragmentation, glioma, shallow WGS