Path-66. seq-ing the sines of central nervous system tumors in cerebrospinal fluid dna

Abstract It is often challenging to distinguish cancerous from non-cancerous lesions in the brain using conventional diagnostic approaches. We here introduce an analytic technique called Real-CSF to detect cancers of the central nervous system from evaluation of DNA in the cerebrospinal fluid (CSF). Short interspersed nuclear elements (SINEs) from throughout the genome are PCR-amplified with a single primer pair and the PCR products are evaluated by next generation sequencing. Real-CSF assesses genome wide copy number alterations in each of 39 chromosome arms as well as focal amplifications of selected oncogenes. Real-CSF was applied to 280 CSF samples and correctly identified 67% of 184 cancers and 96% of 96 non-cancerous brain lesions. CSF analysis was considerably more sensitive than standard of care cytology and plasma cell-free DNA analysis in the same patients. Real-CSF therefore has the capacity to be used in combination with other clinical, radiologic, and laboratory-based data to inform the diagnosis and management of patients with suspected cancers of the brain.