Seq-ing the SINEs of central nervous system tumors in cerebrospinal fluid

Cell Rep Med. 2023 Aug 15;4(8):101148. doi: 10.1016/j.xcrm.2023.101148. Epub 2023 Aug 7.


It is often challenging to distinguish cancerous from non-cancerous lesions in the brain using conventional diagnostic approaches. We introduce an analytic technique called Real-CSF (repetitive element aneuploidy sequencing in CSF) to detect cancers of the central nervous system from evaluation of DNA in the cerebrospinal fluid (CSF). Short interspersed nuclear elements (SINEs) 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 as well as focal amplifications of selected oncogenes. Real-CSF was applied to 280 CSF samples and correctly identified 67% of 184 cancerous 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Central Nervous System
  • Central Nervous System Neoplasms* / cerebrospinal fluid
  • Central Nervous System Neoplasms* / diagnosis
  • Central Nervous System Neoplasms* / genetics
  • Humans
  • Nucleic Acid Amplification Techniques
  • Polymerase Chain Reaction / methods
  • Short Interspersed Nucleotide Elements