Author:
Wang Yuxuan,Springer Simeon,Zhang Ming,McMahon K. Wyatt,Kinde Isaac,Dobbyn Lisa,Ptak Janine,Brem Henry,Chaichana Kaisorn,Gallia Gary L.,Gokaslan Ziya L.,Groves Mari L.,Jallo George I.,Lim Michael,Olivi Alessandro,Quinones-Hinojosa Alfredo,Rigamonti Daniele,Riggins Greg J.,Sciubba Daniel M.,Weingart Jon D.,Wolinsky Jean-Paul,Ye Xiaobu,Oba-Shinjo Sueli Mieko,Marie Suely K. N.,Holdhoff Matthias,Agrawal Nishant,Diaz Luis A.,Papadopoulos Nickolas,Kinzler Kenneth W.,Vogelstein Bert,Bettegowda Chetan
Abstract
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.
Funder
Burroughs Wellcome Fund
Alex's Lemonade Stand Foundation for Childhood Cancer
Pediatric Brain Tumor Foundation
Doris Duke Charitable Foundation
Virginia and D.K. Ludwig Fund for Cancer Research
Publisher
Proceedings of the National Academy of Sciences