Evaluating cancer of the central nervous system through next-generation sequencing of cerebrospinal fluid Journal Article


Authors: Pentsova, E. I.; Shah, R. H.; Tang, J.; Boire, A.; You, D.; Briggs, S.; Omuro, A.; Lin, X.; Fleisher, M.; Grommes, C.; Panageas, K. S.; Meng, F.; Selcuklu, S. D.; Ogilvie, S.; Distefano, N.; Shagabayeva, L.; Rosenblum, M.; DeAngelis, L. M.; Viale, A.; Mellinghoff, I. K.; Berger, M. F.
Article Title: Evaluating cancer of the central nervous system through next-generation sequencing of cerebrospinal fluid
Abstract: Purpose: Cancer spread to the central nervous system (CNS) often is diagnosed late and is unresponsive to therapy. Mechanisms of tumor dissemination and evolution within the CNS are largely unknown because of limited access to tumor tissue. Materials and Methods: We sequenced 341 cancer-associated genes in cell-free DNA from cerebrospinal fluid (CSF) obtained through routine lumbar puncture in 53 patients with suspected or known CNS involvement by cancer. Results: We detected high-confidence somatic alterations in 63% (20 of 32) of patients with CNS metastases of solid tumors, 50% (six of 12) of patients with primary brain tumors, and 0% (zero of nine) of patients without CNS involvement by cancer. Several patients with tumor progression in the CNS during therapy with inhibitors of oncogenic kinases harbored mutations in the kinase target or kinase bypass pathways. In patients with glioma, the most common malignant primary brain tumor in adults, examination of cellfree DNA uncovered patterns of tumor evolution, including temozolomide-associated mutations. Conclusion: The study shows that CSF harbors clinically relevant genomic alterations in patients with CNS cancers and should be considered for liquid biopsies to monitor tumor evolution in the CNS. © 2016 by American Society of Clinical Oncology.
Journal Title: Journal of Clinical Oncology
Volume: 34
Issue: 20
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2016-07-10
Start Page: 2404
End Page: 2415
Language: English
DOI: 10.1200/jco.2016.66.6487
PROVIDER: scopus
PUBMED: 27161972
PMCID: PMC4981784
DOI/URL:
Notes: Article -- Export Date: 2 August 2016 -- Source: Scopus
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MSK Authors
  1. Marc Rosenblum
    246 Rosenblum
  2. Antonio Marcilio Padula Omuro
    167 Omuro
  3. Christian Grommes
    48 Grommes
  4. Katherine S Panageas
    312 Panageas
  5. Agnes Viale
    203 Viale
  6. Michael Forman Berger
    373 Berger
  7. Martin Fleisher
    229 Fleisher
  8. Adrienne Boire
    19 Boire
  9. Shahiba Q Ogilvie
    11 Ogilvie
  10. Samuel Royden Briggs
    14 Briggs
  11. Ronak Hasmukh Shah
    42 Shah
  12. Daoqi You
    20 You
  13. Xuling   Lin
    9 Lin
  14. Jiabin   Tang
    3 Tang
  15. Fanli   Meng
    2 Meng