Released Tumor DNA in the CSF for the Diagnosis and Monitoring of Pediatric Brain Tumors

Email Principal Investigator
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Chetan Bettegowda

CBTN Samples Used


CBTN Participants


CBTN Samples


Alex's Lemonade Stand Foundation

NCI U01CA230691-01

NCI CA230400-01

About this


One of the challenges in neuro-oncology, which is particularly germane to the pediatric population, is the lack of robust biomarkers that can be used to monitor disease burden. The primary modality for diagnosing disease onset, persistence or progression is radiographic imaging with computed tomography (CT) and magnetic resonance imaging (MRI). Both of these imaging modalities only allow clinicians to infer disease burden from anatomical changes. They, unfortunately, do not quantify the level of disease, nor can they differentiate true areas of cancer from treatment related changes. Given the challenges with imaging children and the inherent limitations of existing modalities, the need for novel adjunct biomarkers is striking.

In addition, lesions arising from eloquent portions of the brain and spinal cord present significant challenges for surgeons. Obtaining diagnostic tissue in these cases puts children at tremendous risk of permanent neurological deficit. Having ancillary tests that could obviate the need for surgery would be of tremendous utility.

Our laboratory has been interested in developing cancer specific biomarkers for the last three years. One line of investigation that we have been pursuing is the detection of cell free, DNA shed from tumor cells into body fluids such as plasma and cerebrospinal fluid (CSF).

While it would be ideal to have a simple plasma based test that can detect circulating tumor DNA (ctDNA) in children with central nervous system (CNS) tumors, we have found that levels of ctDNA in brain tumor patients are extraordinarily low. However, we recently demonstrated that levels of tumor derived DNA are significantly enriched in the CSF of individuals with brain tumors, including medulloblastoma. The levels of tumor derived DNA are 10-100x higher in the CSF than in the plasma of brain tumor patients. CSF has the potential to act as a “liquid biopsy” for children with medulloblastoma. Potential applications of CSF-tDNA detection include assessment of minimal residual disease, disease burden, drug resistance, molecular composition and tumor evolution. We have successfully shown that tumor derived DNA can be used for these purposes in other tumor types and hope to extend our findings to medulloblastoma.

Ask The


Ask the scientists

What are the goals of this project?

The goal of this project is to test CSF from 25 children with medulloblastoma for levels of CSF-tDNA and correlate with disease status as identified by conventional radiographic and clinical data.

What is the impact of this project?

If successful, these data will then be used to generate a larger scale study that can be used to bring CSF-tDNA sampling into clinical utility.

Why the CBTN request is important to this project?

The CBTN has a rare collection of medulloblastoma CSF, with matched tumor and blood tissue. For us to perform our assays to detect CSF-tDNA, we ideally will need all three tissues, which is difficult to accrue at any one medical center given the rarity of medulloblastoma.

Specimen Data

The Children's Brain Tumor Network contributed to this project by providing 5 cerebral spinal fluid samples for a pilot cohort.