Tracking tumour evolution in glioma through liquid biopsies of cerebrospinal fluid

Alexandra M. Miller, Ronak H. Shah, Elena I. Pentsova, Maryam Pourmaleki, Samuel Briggs, Natalie Distefano, Youyun Zheng, Anna Skakodub, Smrutiben A. Mehta, Carl Campos, Wan-Ying Hsieh, S. Duygu Selcuklu, Lilan Ling, Fanli Meng, Xiaohong Jing, Aliaksandra Samoila, Tejus A. Bale, Dana W. Y. Tsui, Christian Grommes, Agnes Viale, Mark M. Souweidane, Viviane Tabar, Cameron W. Brennan, Anne S. Reiner, Marc Rosenblum, Katherine S. Panageas, Lisa M. DeAngelis, Robert J. Young, Michael F. Berger () and Ingo K. Mellinghoff ()
Additional contact information
Alexandra M. Miller: Memorial Sloan Kettering Cancer Center
Ronak H. Shah: Memorial Sloan Kettering Cancer Center
Elena I. Pentsova: Memorial Sloan Kettering Cancer Center
Maryam Pourmaleki: Memorial Sloan Kettering Cancer Center
Samuel Briggs: Memorial Sloan Kettering Cancer Center
Natalie Distefano: Memorial Sloan Kettering Cancer Center
Youyun Zheng: Memorial Sloan Kettering Cancer Center
Anna Skakodub: Memorial Sloan Kettering Cancer Center
Smrutiben A. Mehta: Memorial Sloan Kettering Cancer Center
Carl Campos: Memorial Sloan Kettering Cancer Center
Wan-Ying Hsieh: Memorial Sloan Kettering Cancer Center
S. Duygu Selcuklu: Memorial Sloan Kettering Cancer Center
Lilan Ling: Memorial Sloan Kettering Cancer Center
Fanli Meng: Memorial Sloan Kettering Cancer Center
Xiaohong Jing: Memorial Sloan Kettering Cancer Center
Aliaksandra Samoila: Memorial Sloan Kettering Cancer Center
Tejus A. Bale: Memorial Sloan Kettering Cancer Center
Dana W. Y. Tsui: Memorial Sloan Kettering Cancer Center
Christian Grommes: Memorial Sloan Kettering Cancer Center
Agnes Viale: Memorial Sloan Kettering Cancer Center
Mark M. Souweidane: Memorial Sloan Kettering Cancer Center
Viviane Tabar: Memorial Sloan Kettering Cancer Center
Cameron W. Brennan: Memorial Sloan Kettering Cancer Center
Anne S. Reiner: Memorial Sloan Kettering Cancer Center
Marc Rosenblum: Memorial Sloan Kettering Cancer Center
Katherine S. Panageas: Memorial Sloan Kettering Cancer Center
Lisa M. DeAngelis: Memorial Sloan Kettering Cancer Center
Robert J. Young: Memorial Sloan Kettering Cancer Center
Michael F. Berger: Memorial Sloan Kettering Cancer Center
Ingo K. Mellinghoff: Memorial Sloan Kettering Cancer Center

Nature, 2019, vol. 565, issue 7741, 654-658

Abstract: 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.

Date: 2019
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41586-019-0882-3 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:565:y:2019:i:7741:d:10.1038_s41586-019-0882-3

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/s41586-019-0882-3

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().