Extending the Liquid Biopsy Concept from Blood to Cerebrospinal Fluid
Sprecher:Dr. Cäcilia Köstler und Dr. Bernhard Polzer
In patients with leptomeningeal metastases (LM), cancer cells have disseminated to the brain and colonize the meninges. Unfortunately, patients affected with LM are often at a late stage of the disease with dismal prognosis. By investigating cerebrospinal fluid (CSF), low numbers of disseminated cancer cells (DCCs) and DNA released from cancer and normal cells (cell-free DNA; cfDNA) can be detected. To develop innovative applications for predictive biomarkers, we extended our concept for “molecular Liquid Biopsy” from blood to CSF.
As a proof of principle, CSF samples of patients with different primary cancer entities and suspected LM were processed to collect molecular information on the disease. DCCs could be enriched by FDA-approved EpCAM-ferrofluid based CellSearch® technology and isolated as single cells. After whole genome amplification these cells could be confirmed as tumor cells via copy number alteration (CNA) profiling. The parallel isolation and amplification of cfDNA from the same sample achieved subsidiary results. By DEPArray™ analysis of FFPE material derived from primary tumor or different metastatic sites, also brain, the CNA profiles could support thesis of heterogeneity in the tumor environment. In the future, this workflow presents an option for molecular diagnosis in clinical routine and could be utilized to obtain fundamental insights into treatment options for these patients.