Detection of tumor-derived DNA in cerebrospinal fluid of patients with primary tumors of the brain and spinal cord

Yuxuan Wang, Simeon Springer, Ming Zhang, K. Wyatt McMahon, Isaac Kinde, Lisa Dobbyn, Janine Ptak, Henry Brem, Kaisorn Chaichana, Gary L. Gallia, Ziya L. Gokaslan, Mari L. Groves, George I. Jallo, Michael Lim, Alessandro Olivi, Alfredo Quinones-Hinojosa, Daniele Rigamonti, Greg J. Riggins, Daniel M. Sciubba, Jon D. WeingartJean Paul Wolinsky, Xiaobu Ye, Sueli Mieko Oba-Shinjo, Suely K.N. Marie, Matthias Holdhoff, Nishant Agrawal, Luis A. Diaz, Nickolas Papadopoulos, Kenneth W. Kinzler, Bert Vogelstein*, Chetan Bettegowda

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

300 Scopus citations


Cell-free DNA shed by cancer cells has been shown to be a rich source of putative tumor-specific biomarkers. Because cell-free DNA from brain and spinal cord tumors cannot usually be detected in the blood, we studied whether the cerebrospinal fluid (CSF) that bathes the CNS is enriched for tumor DNA, here termed CSF-tDNA. We analyzed 35 primary CNS malignancies and found at least one mutation in each tumor using targeted or genome-wide sequencing. Using these patient-specific mutations as biomarkers, we identified detectable levels of CSF-tDNA in 74% [95% confidence interval (95% CI) = 57-88%] of cases. All medulloblastomas, ependymomas, and high-grade gliomas that abutted a CSF space were detectable (100% of 21 cases; 95% CI = 88-100%), whereas no CSF-tDNA was detected in patients whose tumors were not directly adjacent to a CSF reservoir (P < 0.0001, Fisher's exact test). These results suggest that CSF-tDNA could be useful for the management of patients with primary tumors of the brain or spinal cord.

Original languageEnglish (US)
Pages (from-to)9704-9709
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number31
StatePublished - Aug 4 2015


  • Biomarker
  • CNS tumors
  • CSF-tDNA

ASJC Scopus subject areas

  • General


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