Interrogating malignant gliomas using released tumor DNA in cerebrospinal fluid

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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.