Cerebrospinal fluid as a liquid biopsy for molecular characterization of brain metastasis in patients with non-small cell lung cancer

• DOI: 10.1016/j.lungcan.2023.107292
• Publication Date: 2023-07-03T21:47:14Z
• Authors: Georgios Tsakonas; Vasisht Tadigotla; Sudipto K. Chakra...; Giuseppe Stragliotto; Dalin Chan; Rolf Lewensohn; Wei Yu; Johan K. Skog; Per Hydbring; Simon Ekman
• Keywords: Liquid biopsy

Non-small cell lung cancer (NSCLC) with brain metastases (BM) is a challenging clinical issue poor prognosis. No data exist regarding extensive genetic analysis of cerebrospinal fluid (CSF) and its correlation to associated tumor compartments.We designed study across multiple NSCLC patients matched material from four compartments; primary tumor, BM, plasma CSF. We performed enrichment-based targeted next-generation sequencing ctDNA exosomal RNA in CSF compared the outcome solid compartments.An average 105 million reads per sample was generated fractions mapped exceeding 99% all samples mean coverage above 10,000x. observed high degree overlap variants between BM. Variants specific for BM/CSF compartment included in-frame deletions AR, FGF10 TSC1 missense mutations HNF1a, CD79B, BCL2, MYC, TSC2, TET2, NRG1, MSH3, NOTCH3, VHL EGFR.Our approach combining analyses presents potential surrogate BM biopsy. The that were only CNS compartments could serve as targets individually tailored therapies