Interrogating malignant gliomas using released tumor DNA in cerebrospinal fluid

PROJECT SUMMARY
There are no biomarkers that are currently used in the management of high-grade gliomas.
Therefore, patients are often required to undergo invasive biopsies or surgical resection to
differentiate disease progression from treatment related changes, quantify disease burden and
track the molecular evolution of these difficult to treat cancers. In work performed to date, we
have been able to demonstrate that CSF is a rich reservoir for tumor derived DNA. We are now
expanding upon that work to develop a multi-analyte assay that will incorporate copy number
changes, sub-chromosomal changes and somatic mutations. We anticipate that by looking at
multiple analytes we will be able to improve sensitivity of the assay while also being able to have
a more wholistic understanding of the cancer genotype. The specificity of this multi-analyte assay
will be tested using CSF from individuals without cancer. In the short term, we anticipate that this
approach will allow us to generate personalized biomarkers capable of tracking brain cancers and
providing insights into the tumor genotype, thereby allowing clinicians to make more informed
decisions in real-time. In the long term, we anticipate that we can gain a broader understanding of
the CSF DNA composition in non-neoplastic states, such as multiple sclerosis, neurosarcoidosis
or infection. This could have broad ranging impact on our ability to diagnose and monitor other
disorders impacting the brain.

Grant Number: 5R37CA230400-07
NIH Institute/Center: NIH
Principal Investigator: CHETAN BETTEGOWDA