Detection of tumor-derived DNA in cerebrospinal fluid (CSF) of patients with primary tumors of the brain and spinal cord
Authors:
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 Weingart, Jean-Paul Wolinsky, Xiaobu Ye, Sueli Mieko Oba-Shinjo, Suely K N Marie, Matthias Holdhoff, Nishant Agrawal, Luis A Diaz Jr, Nickolas Papadopoulos, Kenneth W Kinzler, Bert Vogelstein, Chetan Bettegowda
Journal:
Proc Natl Acad Sci U S A. 2015 Aug 4;112(31):9704-9. doi: 10.1073/pnas.1511694112.Epub 2015 Jul 20.
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.
Demonstrating the clinical utility of genomic profiling using cerebrospinal fluid to inform management of central nervous system tumors – a meta analysis of the literature
Authors:
Sakshi Khurana, Qian Nie, Kala F. Schilter, Honey V. Reddi
Journal:
The Journal of Liquid Biopsy, July 2025.
Abstract:
Purpose
Meta-analysis of literature was performed to gain an understanding of the performance of genomic profiling assays in cerebrospinal fluid (CSF) for the diagnosis and management of CNS cancers.
Methods
Using PRISMA methodology, PubMed was searched with the following search terms; “CSF and liquid biopsy” and “cerebrospinal fluid, liquid biopsy, mutations.” Key data fields such as DNA input, technologies used, biomarkers evaluated, types of CNS tumors, sensitivity and specificity, and performance outcomes were analyzed. Studies were excluded if they did not evaluate cancer, use CSF or molecular test methods, had <10 patients, involved pediatric cases or were review articles.
Results
A total of 63 studies were included in the analysis with a majority using ctDNA (n = 38) and targeted NGS panels (n = 45) with both sensitivity and specificity being reported in 24 studies. Of the samples sequenced, 76 % of the primary cancers were gliomas with lung cancer making up 67 % of the metastatic cancers. The Belay Summit™ test performed significantly better in both primary and metastatic CNS cancers with 88 % and 95 % sensitivity respectively compared to studies that used NGS with 6 of the 24 demonstrating a median sensitivity of 47 ± 1.95 % for primary and 7 of 24 demonstrating a median sensitivity of 71 ± 0.76 % for metastatic cancers.
Conclusions
CSF does have potential to inform treatment and management of CNS tumors. For a CSF based molecular test to be highly sensitive and specific, key considerations include panel content, methodology used, the type of variants being evaluated and the inclusion of true negative controls.