# Circulating Cell-Free DNA as a Personalized Biomarker to Diagnose and Monitor Glioblastoma

> **NIH NIH R37** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2020 · $348,844

## Abstract

PROJECT SUMMARY/ABSTRACT
Glioblastoma (GBM) is the most common and most aggressive adult primary brain tumor. Regardless of
therapy, the median survival time is less than 15 months as GBM nearly always recurs. Diagnosing GBM
currently depends on acquiring tumor tissue for histologic examination to differentiate GBM from other types of
brain lesions with a similar imaging appearance. Detecting GBM recurrence is also challenging as treatment
effects such as pseudoprogression and radiation necrosis mimic recurrent disease. Thus, risk-associated
diagnostic invasive procedures remain a critical aspect of GBM patient care even though surgically acquired
neurologic deficits may reduce an already short survival time. Therefore, a non-invasive approach to diagnose
GBM and identify true recurrence has the potential to directly impact patient care throughout the entire disease
course. DNA released from cells during programmed cell death, termed cell-free DNA, is an emerging
biomarker for diagnosing human cancers and monitoring response to therapy. Detection of tumor-derived cell-
free DNA in plasma, also known as circulating tumor DNA (ctDNA), has previously been largely unsuccessful
in humans with GBM due to an inability to find the ctDNA amongst the abundant background of normally
occurring cell-free DNA. The large intra- and inter-tumor genetic heterogeneity of GBM has hindered searches
for specific tumor variants in cell-free DNA, while the rarity of GBM to metastasize beyond the central nervous
system has considerably restricted the quantity of ctDNA present. However, our uncovering of ctDNA in a
xenograft brain tumor model using human GBM stem-like cells strongly supports the feasibility of detecting
GBM-derived ctDNA in humans. Moreover, our previous success in the animal model provides direction for the
human translation – reducing or eliminating noise associated with next-generation sequencing (NGS) that
interferes with the detection of very low frequency variants is necessary to allow searches for ctDNA that are
not dependent on a priori knowledge of solid tumor variants. In this proposal, we attenuate NGS-related noise
and demonstrate the unbiased detection of GBM-derived ctDNA at time of initial diagnosis and at recurrence.
We also show that identification of GBM solid tumor DNA variants in ctDNA is enhanced by reducing errors
associated with NGS to improve sampling of the solid tumor genetic heterogeneity typical of GBM. Therefore,
this proposal seeks to translate plasma cell-free DNA as a biomarker to detect GBM in humans by suppressing
errors associated with NGS to improve variant detection at very low allele frequencies. The successful
application of ctDNA biomarkers to non-invasively assess GBM will directly affect patient care by enabling the
optimization of clinical management prior to or instead of risk-associated invasive diagnostic procedures.

## Key facts

- **NIH application ID:** 9864833
- **Project number:** 1R37CA246183-01
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** Hunter Reeve Underhill
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $348,844
- **Award type:** 1
- **Project period:** 2020-02-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9864833

## Citation

> US National Institutes of Health, RePORTER application 9864833, Circulating Cell-Free DNA as a Personalized Biomarker to Diagnose and Monitor Glioblastoma (1R37CA246183-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9864833. Licensed CC0.

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