Detection of Human Brain Cancers using Genomic and Immune Cell Characterization of Cerebrospinal Fluid through CSF-BAM

Patients with radiographically detectable lesions in their brain or other symptoms compatible with brain tumors pose challenges for diagnosis. The only definitive way to diagnose such patients is through brain biopsy, an invasive and dangerous procedure. In this study, we present a new workflow termed “CSF-BAM” that simultaneously identifies B-cell or T-cell receptor sequences, aneuploidy, and mutations using amplification of both strands of the DNA from cerebrospinal fluid (CSF) samples. We applied CSF-BAM to a validation set of 209 samples from patients with brain cancers. Among the 129 samples from patients with the most common aggressive cancer types, the sensitivity of detection was 81%. None of 30 CSF-BAM assays were positive in CSF samples from patients without brain cancers (100% specificity). CSF-BAM provides an integrated approach to identify neoplasia in the central nervous system, provides information about the genetics and immune environment, and has the potential to inform patient management. Significance: There is a paucity of technologies beyond surgical biopsy that can accurately diagnose central nervous system neoplasms. We developed a novel, sensitive, and highly specific assay that can detect brain cancers by comprehensively identifying somatic mutations, chromosomal copy-number changes, and adaptive immunoreceptor repertoires from samples of CSF.