Tracking tumour evolution in glioma through liquid biopsies of cerebrospinal fluid Research Letter


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.
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
PMCID: PMC6457907
DOI/URL:
Notes: Source: Scopus
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MSK Authors
  1. Anne S Reiner
    248 Reiner
  2. Robert J Young
    228 Young
  3. Viviane S Tabar
    225 Tabar
  4. Cameron Brennan
    226 Brennan
  5. Marc Rosenblum
    424 Rosenblum
  6. Elena Pentsova
    132 Pentsova
  7. Christian Grommes
    150 Grommes
  8. Katherine S Panageas
    512 Panageas
  9. Agnes Viale
    245 Viale
  10. Xiaohong Jing
    21 Jing
  11. Michael Forman Berger
    765 Berger
  12. Carl Campos
    37 Campos
  13. Lilan Ling
    44 Ling
  14. Samuel Royden Briggs
    18 Briggs
  15. Ronak Hasmukh Shah
    72 Shah
  16. Aliaksandra Samoila
    23 Samoila
  17. Alexandra Miller
    74 Miller
  18. Fanli   Meng
    27 Meng
  19. Wai Yi   Tsui
    50 Tsui
  20. Wan-Ying Hsieh
    5 Hsieh
  21. Tejus Bale
    122 Bale
  22. Smrutiben A Mehta
    3 Mehta
  23. Youyun Zheng
    10 Zheng