ROCHESTER, Minn., and PHOENIX — A Mayo Clinic study published in the Journal of Neuro-Oncology suggests that analyzing DNA in cerebrospinal fluid could provide another source of information when MRI cannot provide a clear brain tumor diagnosis or obtaining tissue through biopsy is difficult or potentially unsafe.
The study included 76 patients facing one of three challenging clinical scenarios:
- An abnormality in the brain or spinal cord without a diagnosis;
- Imaging changes that could reflect either tumor growth or treatment effects; or
- Suspected leptomeningeal disease, in which cancer spreads to the membranes and fluid surrounding the brain and spinal cord.
The investigation detected tumor-associated DNA in 20 patients (26%). For those patients, the findings provided another piece of evidence that clinicians could consider alongside imaging, pathology and the patient's overall clinical picture.
Why can MRI and tissue biopsy leave unanswered questions in brain tumor care?
MRI and tissue biopsy remain essential for diagnosing and monitoring cancers involving the brain and spinal cord. But each has limitations.
Changes on an MRI can often look similar whether they are caused by cancer, inflammation or the effects of treatment. In other cases, a lesion's location may make obtaining tissue through biopsy difficult or unsafe.
Researchers are increasingly studying whether tumor-related material released into body fluids can provide another source of information. A liquid biopsy looks for material such as tumor DNA in a body fluid rather than in a tissue sample. Most liquid biopsies use blood.
For brain tumors, however, the blood-brain barrier — a protective boundary that controls what passes between the bloodstream and the brain — can limit how much tumor DNA reaches the bloodstream, making it difficult to detect.
Mayo Clinic researchers are therefore studying cerebrospinal fluid, or CSF, the clear fluid that surrounds the brain and spinal cord. Tumor cells can release small DNA fragments into this fluid. These fragments, known as cell-free DNA, may contain genetic changes associated with a tumor.
CSF can be collected through a lumbar puncture , also known as a spinal tap, in which a thin needle is inserted into the lower back. Researchers then analyze the DNA fragments in the sample for changes in individual genes and broader DNA patterns associated with tumors.
"In some cases, this CSF DNA approach has provided important diagnostic information when obtaining tissue safely was not an option," says Terry Burns, M.D., Ph.D. , a Mayo Clinic neurosurgeon and senior author of the study.
What did Mayo Clinic researchers find in CSF?
Patients in this study represented three clinical groups:
- 35 had a brain or spinal cord abnormality whose cause was uncertain;
- 21 had imaging changes that could represent either tumor progression or treatment-related effects; and
- 20 were being evaluated for leptomeningeal disease
Across the 76 patients, the analysis found signs of tumor DNA in 20 patients. In 29 patients, the samples contained enough DNA for analysis, but no signs of tumor DNA were detected. The remaining 27 samples did not contain enough usable DNA to complete the analysis.
A negative result did not rule out cancer. The amount of tumor DNA in CSF can vary, and some samples may contain too little tumor DNA for the analysis to detect. Researchers are working to improve the analysis of samples containing very small amounts of DNA.
How could CSF DNA testing inform brain tumor care?
Analyzing cell-free DNA in CSF could provide more than a sign that tumor material is present. The DNA fragments may also contain information about a tumor's genetic features. In the future, that information could help care teams identify clinical trials or treatments that target specific genetic changes.
The test used in this study remains investigational. When it can be obtained safely, tumor tissue remains the gold standard for making a definitive diagnosis. Researchers are working to determine which patients may benefit most from CSF DNA analysis and when the approach could add useful information to imaging, pathology and other established methods.
"Our goal is for CSF cell-free DNA testing to provide patients and their care teams with diagnostic insights when answers may otherwise be difficult to obtain," says Cecile Riviere-Cazaux, a Mayo Clinic Alix School of Medicine student in Rochester and co-first author of the study. "As we gain more experience, we hope it will also help connect patients with clinical trials and personalized treatment options."
Mayo Clinic researchers are now working to improve the analysis of samples containing very small amounts of tumor DNA and to determine how changes in DNA and other biomarkers over time could help show whether a tumor is responding to treatment.
For a complete list of authors, disclosures and funding, review the study .
