Brain tumor mutations detected in cerebral spinal fluid

Clin Chem. 2015 Mar;61(3):514-22. doi: 10.1373/clinchem.2014.235457. Epub 2015 Jan 20.


Background: Detecting tumor-derived cell-free DNA (cfDNA) in the blood of brain tumor patients is challenging, presumably owing to the blood-brain barrier. Cerebral spinal fluid (CSF) may serve as an alternative "liquid biopsy" of brain tumors by enabling measurement of circulating DNA within CSF to characterize tumor-specific mutations. Many aspects about the characteristics and detectability of tumor mutations in CSF remain undetermined.

Methods: We used digital PCR and targeted amplicon sequencing to quantify tumor mutations in the cfDNA of CSF and plasma collected from 7 patients with solid brain tumors. Also, we applied cancer panel sequencing to globally characterize the somatic mutation profile from the CSF of 1 patient with suspected leptomeningeal disease.

Results: We detected tumor mutations in CSF samples from 6 of 7 patients with solid brain tumors. The concentration of the tumor mutant alleles varied widely between patients, from <5 to nearly 3000 copies/mL CSF. We identified 7 somatic mutations from the CSF of a patient with leptomeningeal disease by use of cancer panel sequencing, and the result was concordant with genetic testing on the primary tumor biopsy.

Conclusions: Tumor mutations were detectable in cfDNA from the CSF of patients with different primary and metastatic brain tumors. We designed 2 strategies to characterize tumor mutations in CSF for potential clinical diagnosis: the targeted detection of known driver mutations to monitor brain metastasis and the global characterization of genomic aberrations to direct personalized cancer care.

MeSH terms

  • Brain Neoplasms / cerebrospinal fluid
  • Brain Neoplasms / genetics*
  • DNA / blood
  • DNA / cerebrospinal fluid
  • DNA / genetics*
  • DNA, Neoplasm / blood
  • DNA, Neoplasm / cerebrospinal fluid
  • DNA, Neoplasm / genetics*
  • Exome
  • Humans
  • Mutation*
  • Polymerase Chain Reaction / methods


  • DNA, Neoplasm
  • DNA