title: Brain tumor mutations detected in cerebral spinal fluid.
abstract: 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.
authors.affiliation: Department of Bioengineering.
authors.forename: Wenying
authors.initials: W
authors.lastname: Pan
authors.affiliation: Department of Bioengineering, Department of Pathology and Laboratory Medicine, University of California-San Francisco, San Francisco, CA.
authors.forename: Wei
authors.initials: W
authors.lastname: Gu
authors.affiliation: Department of Neurology, Stanford University, Stanford, CA;
authors.forename: Seema
authors.initials: S
authors.lastname: Nagpal
authors.affiliation: Department of Neurosurgery, and quake@stanford.edu mghayden@stanford.edu.
authors.forename: Melanie Hayden
authors.initials: MH
authors.lastname: Gephart
authors.affiliation: Department of Bioengineering, quake@stanford.edu mghayden@stanford.edu.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Quake
mesh_terms: D001932:Brain Neoplasms / Q000134:cerebrospinal fluid / Q000235:genetics*; D004247:DNA / Q000097:blood / Q000134:cerebrospinal fluid / Q000235:genetics*; D004273:DNA, Neoplasm / Q000097:blood / Q000134:cerebrospinal fluid / Q000235:genetics*; D059472:Exome; D006801:Humans; D009154:Mutation; D016133:Polymerase Chain Reaction / Q000379:methods
chemical_list: D004273:DNA, Neoplasm; D004247:DNA