Cerebrospinal fluid cell-free tumour DNA as a liquid biopsy for primary brain tumours and central nervous system metastases

Ann Oncol. 2019 Feb 1;30(2):211-218. doi: 10.1093/annonc/mdy544.


Challenges in obtaining tissue specimens from patients with brain tumours limit the diagnosis and molecular characterisation and impair the development of better therapeutic approaches. The analysis of cell-free tumour DNA in plasma (considered a liquid biopsy) has facilitated the characterisation of extra-cranial tumours. However, cell-free tumour DNA in plasma is limited in quantity and may not reliably capture the landscape of genomic alterations of brain tumours. Here, we review recent work assessing the relevance of cell-free tumour DNA from cerebrospinal fluid in the characterisation of brain cancer. We focus on the advances in the use of the cerebrospinal fluid as a source of cell-free tumour DNA to facilitate diagnosis, reveal actionable genomic alterations, monitor responses to therapy, and capture tumour heterogeneity in patients with primary brain tumours and brain and leptomeningeal metastases. Profiling cerebrospinal fluid cell-free tumour DNA provides the opportunity to precisely acquire and monitor genomic information in real time and guide precision therapies.

Keywords: brain cancer; brain metastasis; cerebrospinal fluid; circulating cell-free tumour DNA; glioblastoma; liquid biopsy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Biomarkers, Tumor / cerebrospinal fluid
  • Biomarkers, Tumor / genetics*
  • Brain Neoplasms / cerebrospinal fluid
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology*
  • Central Nervous System Neoplasms / cerebrospinal fluid
  • Central Nervous System Neoplasms / genetics
  • Central Nervous System Neoplasms / secondary*
  • Circulating Tumor DNA / cerebrospinal fluid
  • Circulating Tumor DNA / genetics*
  • DNA, Neoplasm / cerebrospinal fluid
  • DNA, Neoplasm / genetics*
  • Humans
  • Liquid Biopsy / methods*
  • Neoplasm Staging


  • Biomarkers, Tumor
  • Circulating Tumor DNA
  • DNA, Neoplasm