Tracking tumour evolution in glioma through liquid biopsies of cerebrospinal fluid

被引：424

作者：

Miller, Alexandra M. ^{[1
]}

Shah, Ronak H. ^{[2
,3
,12
]}

Pentsova, Elena I. ^{[1
]}

Pourmaleki, Maryam ^{[4
]}

Briggs, Samuel ^{[1
]}

Distefano, Natalie ^{[5
]}

Zheng, Youyun ^{[2
,3
]}

Skakodub, Anna ^{[1
]}

Mehta, Smrutiben A. ^{[4
]}

Campos, Carl ^{[4
]}

Hsieh, Wan-Ying ^{[4
]}

Selcuklu, S. Duygu ^{[3
]}

Ling, Lilan ^{[3
]}

Meng, Fanli ^{[3
]}

Jing, Xiaohong ^{[3
]}

Samoila, Aliaksandra ^{[6
]}

Bale, Tejus A. ^{[2
]}

Tsui, Dana W. Y. ^{[2
,3
]}

Grommes, Christian ^{[1
]}

Viale, Agnes ^{[3
]}

Souweidane, Mark M. ^{[5
,7
]}

Tabar, Viviane ^{[5
]}

Brennan, Cameron W. ^{[5
]}

Reiner, Anne S. ^{[8
]}

Rosenblum, Marc ^{[2
]}

Panageas, Katherine S. ^{[8
]}

DeAngelis, Lisa M. ^{[1
]}

Young, Robert J. ^{[9
]}

Berger, Michael F. ^{[2
,3
,4
,10
]}

Mellinghoff, Ingo K. ^{[1
,4
,11
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Dept Neurol, 1275 York Ave, New York, NY 10021 USA

[2] Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10021 USA

[3] Mem Sloan Kettering Canc Ctr, Ctr Mol Oncol, New York, NY USA

[4] Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, 1275 York Ave, New York, NY 10021 USA

[5] Mem Sloan Kettering Canc Ctr, Dept Neurosurg, New York, NY USA

[6] Mem Sloan Kettering Canc Ctr, Dept Lab Med, 1275 York Ave, New York, NY 10021 USA

[7] Weill Cornell Med Coll, Dept Neurol Surg, New York, NY USA

[8] Mem Sloan Kettering Canc Ctr, Dept Epidemiol & Biostat, 1275 York Ave, New York, NY 10021 USA

[9] Mem Sloan Kettering Canc Ctr, Dept Radiol, 1275 York Ave, New York, NY 10021 USA

[10] Weill Cornell Med Coll, Dept Pathol & Lab Med, New York, NY USA

[11] Weill Cornell Med Coll, Dept Pharmacol, New York, NY USA

[12] Northwell Hlth, Dept Pediat, Med Genet & Human Genom, Manhasset, NY USA

来源：

NATURE | 2019年 / 565卷 / 7741期

基金：

美国国家卫生研究院;

关键词：

CENTRAL-NERVOUS-SYSTEM; GENOMIC CHARACTERIZATION; MUTATIONAL LANDSCAPE; GLIOBLASTOMA; CANCER; ARCHITECTURE; ONCOLOGY; REVEALS; DNA;

D O I：

10.1038/s41586-019-0882-3

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 therapy(1,2), but involves brain surgery for tissue collection; repeated tumour biopsies may be necessary for accurate genotyping over the course of the disease(3-10). While the detection of circulating tumour DNA (ctDNA) in the blood of patients with primary brain tumours remains challenging(11,12), sequencing of ctDNA from the cerebrospinal fluid (CSF) may provide an alternative way to genotype gliomas with lower morbidity and cost(13,14). 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 IDH2(1,2), 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.

引用

页码：654 / +

页数：17

共 28 条

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← 1 2 3 →

共 28 条

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Takahashi, Miwako ;

Momose, Toshimitsu ;

Tanaka, Shota ;

Takayanagi, Shunsaku ;

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Nejo, Takahide ;

Takahashi, Satoshi ;

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Saito, Kuniaki ;

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Lepisto, Eva M. ;

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Ozduman, Koray ;

Omay, S. Buelent ;

Sorensen, Eric A. ;

Turcan, Sevin ;

Bakirciglu, Mehmet ;

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Knight, James ;

Sencar, Leman ;

Altinok, Selin ;

Kaulen, Leon D. ;

Guelez, Burcu ;

Timmer, Marco ;

Schramm, Johannes ;

Mishra-Gorur, Ketu ;

Henegariu, Octavian ;

Moliterno, Jennifer ;

Louvi, Angeliki ;

Chan, Timothy A. ;

Tannheimer, Stacey L. ;

Pamir, M. Necmettin ;

Vortmeyer, Alexander O. ;

Bilguvar, Kaya ;

Yasuno, Katsuhito ;

Guenel, Murat .

NATURE GENETICS, 2016, 48 (01) :59-+

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Bettegowda, Chetan ;

Sausen, Mark ;

Leary, Rebecca J. ;

Kinde, Isaac ;

Wang, Yuxuan ;

Agrawal, Nishant ;

Bartlett, Bjarne R. ;

Wang, Hao ;

Luber, Brandon ;

Alani, Rhoda M. ;

Antonarakis, Emmanuel S. ;

Azad, Nilofer S. ;

Bardelli, Alberto ;

Brem, Henry ;

Cameron, John L. ;

Lee, Clarence C. ;

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