Clinical Experience of Cerebrospinal Fluid-Based Liquid Biopsy Demonstrates Superiority of Cell-Free DNA over Cell Pellet Genomic DNA for Molecular Profiling.

摘要: Cell-free DNA (cfDNA) from cerebrospinal fluid (CSF) offers unique opportunities for genomic profiling of tumors involving the central nervous system but remains uncommonly used in clinical practice. We describe our experience using cfDNA CSF routine molecular testing Memorial Sloan Kettering Integrated Mutation Profiling Actionable Cancer Targets (targeting 468 cancer-related genes). In all, 148 samples were assessed, comparing results versus (gDNA; gDNA cell pellets) derived same sample and primary tumor. Of these, 71.6% (106/148) successfully sequenced. Somatic alterations (mutations fusions) observed 70.8% (75/106) samples; 97.3% (73/75) comprised variants confirming involvement by a previously diagnosed tumor, 14.7% (11/75) had additional consistent with therapy-related resistance mechanism, 2.7% (2/75) that independently new primary. Among paired sequencing results, was more frequently positive at least one mutation [43.6% (55/126) 19.8% (25/126)] harbored 1.6× mutations (6.94 4.65; P = 0.005), higher mean variant allele fractions (41.1% 13.0%; P