Multi-omic CSF Assay for the Diagnosis of Brain Cancers

PROJECT SUMMARY Brain imaging with computed tomography (CT) or magnetic resonance imaging (MRI) is becoming increasingly used in clinical practice. In up to 25% of MRI scans, an incidental brain abnormality is identified. The list of potential etiologies for these findings is vast and can include benign conditions such as inflammatory or developmental processes or could also include neoplastic entities such as malignant gliomas. Approximately 17,000 individuals each year are diagnosed with a malignant glioma in the United States and the nearly of these patients will succumb to their disease. Therefore, the need to reliably and quickly distinguish a neoplastic from a non-neoplastic condition is of significant importance. Unfortunately, currently there are no clinically available biomarkers for CNS malignancies. Correctly identifying these abnormalities as non-malignant is important because such patients rarely benefit from surgical biopsy and can almost always be managed non- operatively. And a diagnosis other than CNS malignancy can alleviate much of the anxiety experienced by patients without cancer after imaging. In contrast, patients with cancer could benefit from correct diagnosis by spurring immediate consultation with appropriate neurosurgical and oncology specialists. As a result, there is an pressing and urgent 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). We have developed a robust multi-omic technology, CSF-TumorDx, that can sensitively and specifically detect trace quantities of CSF-tDNA from 1-2 ml of CSF. In this Fast-Track application we will i) establish pre-analytic quality control procedures, ii) determine the analytical sensitivity and specificity of CSF-TumorDx and iii) determine the clinical validity of CSF-TumorDx. At the completion of this grant, Belay Diagnostics will be poised to commercialize the first multi-omic molecular diagnostic for primary brain cancers in a CLIA setting. This could have an immediate impact on the thousands of individuals facing diagnostic uncertainty from a brain lesion identified on imaging.