|Title||Clinical Experience of Cerebrospinal Fluid-Based Liquid Biopsy Demonstrates Superiority of Cell-Free DNA over Cell Pellet Genomic DNA for Molecular Profiling.|
|Publication Type||Journal Article|
|Year of Publication||2021|
|Authors||Bale TA, Yang S-R, Solomon JP, Nafa K, Middha S, Casanova J, Sadowska J, Skakodub A, Ahmad H, Yu HA, Riely GJ, Kris MG, Chandarlapaty S, Rosenblum MK, Gavrilovic I, Karajannis MA, Pentsova E, Miller A, Boire A, Mellinghoff I, Berger MF, Zehir A, Ladanyi M, Benayed R, Arcila ME|
|Journal||J Mol Diagn|
|Date Published||2021 06|
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 clinical experience using cfDNA from CSF for routine molecular testing using Memorial Sloan Kettering Integrated Mutation Profiling of Actionable Cancer Targets (targeting 468 cancer-related genes). In all, 148 cfDNA samples were assessed, comparing results of cfDNA versus genomic DNA (gDNA; gDNA from cell pellets) derived from the same CSF sample and the primary tumor. Of these, 71.6% (106/148) were successfully sequenced. Somatic alterations (mutations and fusions) were observed in 70.8% (75/106) of the samples; 97.3% (73/75) comprised variants confirming central nervous system involvement by a previously diagnosed tumor, 14.7% (11/75) had additional variants consistent with a therapy-related resistance mechanism, and 2.7% (2/75) had variants that independently diagnosed a new primary. Among samples with paired cfDNA and gDNA sequencing results, cfDNA was more frequently positive for at least one mutation [43.6% (55/126) versus 19.8% (25/126)] and harbored 1.6× more mutations (6.94 versus 4.65; P = 0.005), with higher mean variant allele fractions (41.1% versus 13.0%; P < 0.0001). Among mutation-positive cfDNAs, the corresponding gDNA was frequently negative (44.6%; 25/55) or failed sequencing (17.8%; 9/55). Routine molecular profiling of cfDNA is superior to gDNA from CSF, facilitating the capture of mutations at high variant allele frequency, even in the context of a negative cytology.
|Alternate Journal||J Mol Diagn|
|PubMed Central ID||PMC8207471|
|Grant List||P30 CA008748 / CA / NCI NIH HHS / United States |
R35 NS105109 / NS / NINDS NIH HHS / United States
James Solomon, M.D., Ph.D.