Tracking tumour evolution in glioma through liquid biopsies of cerebrospinal fluid Journal Article


Authors: Miller, A. M.; Shah, R. H.; Pentsova, E. I.; Pourmaleki, M.; Briggs, S.; Distefano, N.; Zheng, Y.; Skakodub, A.; Mehta, S. A.; Campos, C.; Hsieh, W. Y.; Selcuklu, S. D.; Ling, L.; Meng, F.; Jing, X.; Samoila, A.; Bale, T. A.; Tsui, D. W. Y.; Grommes, C.; Viale, A.; Souweidane, M. M.; Tabar, V.; Brennan, C. W.; Reiner, A. S.; Rosenblum, M.; Panageas, K. S.; DeAngelis, L. M.; Young, R. J.; Berger, M. F.; Mellinghoff, I. K.
Article Title: Tracking tumour evolution in glioma through liquid biopsies of cerebrospinal fluid
Abstract: Diffuse gliomas are the most common malignant brain tumours in adults and include glioblastomas and World Health Organization (WHO) grade II and grade III tumours (sometimes referred to as lower-grade gliomas). Genetic tumour profiling is used to classify disease and guide therapy1,2, but involves brain surgery for tissue collection; repeated tumour biopsies may be necessary for accurate genotyping over the course of the disease3–10. While the detection of circulating tumour DNA (ctDNA) in the blood of patients with primary brain tumours remains challenging11,12, sequencing of ctDNA from the cerebrospinal fluid (CSF) may provide an alternative way to genotype gliomas with lower morbidity and cost13,14. We therefore evaluated the representation of the glioma genome in CSF from 85 patients with gliomas who underwent a lumbar puncture because they showed neurological signs or symptoms. Here we show that tumour-derived DNA was detected in CSF from 42 out of 85 patients (49.4%) and was associated with disease burden and adverse outcome. The genomic landscape of glioma in the CSF included a broad spectrum of genetic alterations and closely resembled the genomes of tumour biopsies. Alterations that occur early during tumorigenesis, such as co-deletion of chromosome arms 1p and 19q (1p/19q codeletion) and mutations in the metabolic genes isocitrate dehydrogenase 1 (IDH1) or IDH21,2, were shared in all matched ctDNA-positive CSF–tumour pairs, whereas growth factor receptor signalling pathways showed considerable evolution. The ability to monitor the evolution of the glioma genome through a minimally invasive technique could advance the clinical development and use of genotype-directed therapies for glioma, one of the most aggressive human cancers. © 2019, Springer Nature Limited.
Journal Title: Nature
Volume: 565
Issue: 7741
ISSN: 0028-0836
Publisher: Nature Publishing Group  
Date Published: 2019-01-31
Start Page: 654
End Page: 658
Language: English
DOI: 10.1038/s41586-019-0882-3
PUBMED: 30675060
PROVIDER: scopus
DOI/URL:
Notes: Source: Scopus
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MSK Authors
  1. Anne S Reiner
    121 Reiner
  2. Robert J Young
    112 Young
  3. Viviane S Tabar
    120 Tabar
  4. Cameron Brennan
    155 Brennan
  5. Marc Rosenblum
    254 Rosenblum
  6. Christian Grommes
    54 Grommes
  7. Katherine S Panageas
    329 Panageas
  8. Agnes Viale
    205 Viale
  9. Xiaohong Jing
    10 Jing
  10. Michael Forman Berger
    386 Berger
  11. Carl Campos
    22 Campos
  12. Lilan Ling
    39 Ling
  13. Samuel Royden Briggs
    16 Briggs
  14. Ronak Hasmukh Shah
    43 Shah
  15. Aliaksandra Samoila
    13 Samoila
  16. Alexandra Miller
    7 Miller
  17. Fanli   Meng
    3 Meng
  18. Wai Yi   Tsui
    10 Tsui
  19. Wan-Ying Hsieh
    5 Hsieh
  20. Tejus Bale
    2 Bale
  21. Smrutiben A Mehta
    1 Mehta
  22. Youyun Zheng
    1 Zheng