In brain tumors, new use for CSF cfDNA

Summary

Cerebrospinal fluid (CSF) samples are increasingly being used for genomic profiling of brain tumors, offering a less invasive alternative to tissue biopsies. CSF samples provide a higher signal-to-noise ratio for detecting tumor-derived cell-free DNA (cfDNA) compared to plasma samples, making them particularly useful for diagnosing and monitoring brain tumors, including leptomeningeal metastases. The use of CSF cfDNA has shown promise in identifying new primary tumors and detecting tumor recurrence earlier than traditional methods.

Karen Titus

April 2026—It’s hard to mount an argument against the Great Plains. Nor is there much reason to.

But drive across eastern Colorado, Nebraska, Kansas, or the Dakotas, and it is a bona fide thrill to arrive in Wyoming’s northwest corner and see the Grand Tetons rising up in spectacular fashion. After days lost in predictable but necessary miles, what traveler doesn’t marvel at the sight of those jagged peaks and think, This is here, too?!

A similar revelation has been occurring with the use of cerebrospinal fluid samples in the care of patients with brain tumors. These samples are hardly strangers to clinical practice—CSF already has a place in standard of care for many laboratory analyses, including cytology and chemistry.

But its use is also expanding: CSF samples have been shown to be an accessible source of tumor-derived cell-free DNA for use in genomic profiling of central nervous system tumors.

Tissue is often an issue for such tumors. It can be difficult to obtain, and samples are often small and otherwise limited. Moreover, high-grade tumors can be very necrotic. But the need for genomic profiling is urgent, says Tejus Bale, MD, PhD, associate attending pathologist in the Division of Neuropathology and the Division of Diagnostic Molecular Pathology at Memorial Sloan Kettering Cancer Center. “What we need to know in terms of tumor molecular characterization is rapidly expanding,” says Dr. Bale, who also serves as associate training program director of the molecular genetic pathology fellowship.

The Food and Drug Administration has approved IDH-inhibitor therapy for grade two gliomas, for example. Likewise, there is now FDA-approved therapy for H3 K27M-mutant diffuse midline gliomas. Moreover, she says, “The same gamut of targeted therapies that exist for solid tumors throughout the body still apply to the story in the CNS once these tumors metastasize.”

The long-abiding CSF sample now offers “a unique opportunity,” she says, for diagnosing and prognosticating brain tumors. “We are increasingly finding important uses for the cell-free DNA in the CSF.” In some cases, it appears to be a more sensitive prognostic marker. The presence of tumor cells in CSF cytology samples is the gold standard for diagnosis of leptomeningeal metastases, for example, and is considered a poor prognostic indicator for certain tumors, such as medulloblastomas. “The presence of cells is often a harbinger of early tumor recurrence,” says Dr. Bale, “and we’re increasingly finding out that cell-free DNA, or the molecular positive results, precedes the ability to detect cells in many tumor types.”