Clinical experience of cerebrospinal fluid-based liquid biopsy demonstrates superiority of cell-free DNA over cell pellet genomic DNA for molecular profiling Journal Article


Authors: Bale, T. A.; Yang, S. R.; Solomon, J. P.; Nafa, K.; Middha, S.; Casanova, J.; Sadowska, J.; Skakodub, A.; Ahmad, H.; Yu, H. A.; Riely, G. J.; Kris, M. G.; Chandarlapaty, S.; Rosenblum, M. K.; Gavrilovic, I.; Karajannis, M. A.; Pentsova, E.; Miller, A.; Boire, A.; Mellinghoff, I.; Berger, M. F.; Zehir, A.; Ladanyi, M.; Benayed, R.; Arcila, M. E.
Article Title: Clinical experience of cerebrospinal fluid-based liquid biopsy demonstrates superiority of cell-free DNA over cell pellet genomic DNA for molecular profiling
Abstract: 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. © 2021 Association for Molecular Pathology and American Society for Investigative Pathology
Journal Title: Journal of Molecular Diagnostics
Volume: 23
Issue: 6
ISSN: 1525-1578
Publisher: Elsevier Science, Inc.  
Date Published: 2021-06-01
Start Page: 742
End Page: 752
Language: English
DOI: 10.1016/j.jmoldx.2021.03.001
PUBMED: 33781965
PROVIDER: scopus
PMCID: PMC8207471
DOI/URL:
Notes: Article -- Export Date: 1 July 2021 -- Source: Scopus
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MSK Authors
  1. Khedoudja Nafa
    222 Nafa
  2. Marc Rosenblum
    379 Rosenblum
  3. Helena Alexandra Yu
    186 Yu
  4. Marc Ladanyi
    1190 Ladanyi
  5. Gregory J Riely
    504 Riely
  6. Elena Pentsova
    101 Pentsova
  7. Ahmet Zehir
    311 Zehir
  8. Michael Forman Berger
    602 Berger
  9. Maria Eugenia Arcila
    554 Arcila
  10. Mark Kris
    804 Kris
  11. Adrienne Boire
    63 Boire
  12. Alexandra Miller
    34 Miller
  13. Rym Benayed
    167 Benayed
  14. Sumit   Middha
    82 Middha
  15. Tejus Bale
    53 Bale
  16. James Patrick Solomon
    15 Solomon
  17. Hamza Ahmad
    4 Ahmad
  18. Soo Ryum Yang
    28 Yang