# Interrogating malignant gliomas using released tumor DNA in cerebrospinal fluid

> **NIH NIH R37** · JOHNS HOPKINS UNIVERSITY · 2020 · $374,578

## Abstract

PROJECT SUMMARY/ABSTRACT
Approximately 17,000 individuals each year are diagnosed with a malignant glioma in the United States and
the vast majority of these patients will succumb to their disease. Given the lack of clinically available
biomarkers for CNS malignancies, the conventional method for disease monitoring in these patients is
radiographic. Unfortunately, anatomic changes detected by MRI and CT scans are often non-specific and lag
behind progressing or regressing disease. Moreover, it can be difficult to discriminate between treatment
effect and cancer growth with imaging alone. Patients must, therefore, have additional surgeries for definitive
tissue diagnosis or inappropriately wait for radiographic findings to change as their disease progresses
unabated. As a result, there is an incredible need for more sensitive and specific tumor biomarkers in neuro-
oncology.
We and others have shown that most cancers shed cell free molecules of tumor derived DNA into the
circulation and that these molecules can be quantified as a measure of disease burden. Brain tumors are the
exception to the rule and rarely shed detectable levels DNA into the bloodstream. However, we have
provocative data to suggest that malignant gliomas shed cell free molecules of tumor derived DNA into the
cerebrospinal fluid (CSF-tDNA). CSF-tDNA can be distinguished from DNA derived from normal cells by the
presence of disease defining somatic mutations. Levels of CSF-tDNA can be quantified using sensitive digital
sequencing based assays, such “Safe-SeqS”. In Aim 1, we will use Safe-SeqS to quantify CSF-tDNA levels in
longitudinal spinal fluid samples derived from 20 patients with malignant gliomas. We will determine how
closely CSF-tDNA levels correlate with disease status as measured by clinical, radiographic and pathological
findings. If successful, this approach will accurately assess tumor response and identify those patients at
highest risk for recurrence, thus enabling the clinician to alter treatment regimens.
There are also burgeoning data to suggest that all cancers, including malignant gliomas, evolve over time in
response to various selection pressures, including treatment. These genetic changes have important clinical
implications but currently there are no minimally invasive clinical assays that are capable of providing insights
into the glioma genotype. As a result, in Aim 2, we will perform whole exome sequencing directly on the CSF
and compare to exomic sequencing results from matched tumor/normal samples. This will allow us to
understand what fraction of tumor genotype can be detected by analyzing the CSF directly. In order to
determine the background mutation rate in CSF, in Aim 3 we will perform Safe-SeqS directly on the CSF of 50
individuals without any history of cancer. At the completion of this grant, we hope to validate CSF-tDNA as a
candidate biomarker for individuals with malignant glioma and set the stage for large scale clinical trials that
can b...

## Key facts

- **NIH application ID:** 9964496
- **Project number:** 5R37CA230400-03
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** CHETAN BETTEGOWDA
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $374,578
- **Award type:** 5
- **Project period:** 2018-07-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9964496

## Citation

> US National Institutes of Health, RePORTER application 9964496, Interrogating malignant gliomas using released tumor DNA in cerebrospinal fluid (5R37CA230400-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9964496. Licensed CC0.

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