Tracking tumour evolution in glioma through liquid biopsies of cerebrospinal fluid

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 involv...

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Vydáno v:	Nature (London) Ročník 565; číslo 7741; s. 654 - 658
Hlavní autoři:	Miller, Alexandra M., Shah, Ronak H., Pentsova, Elena I., Pourmaleki, Maryam, Briggs, Samuel, Distefano, Natalie, Zheng, Youyun, Skakodub, Anna, Mehta, Smrutiben A., Campos, Carl, Hsieh, Wan-Ying, Selcuklu, S. Duygu, Ling, Lilan, Meng, Fanli, Jing, Xiaohong, Samoila, Aliaksandra, Bale, Tejus A., Tsui, Dana W. Y., Grommes, Christian, Viale, Agnes, Souweidane, Mark M., Tabar, Viviane, Brennan, Cameron W., Reiner, Anne S., Rosenblum, Marc, Panageas, Katherine S., DeAngelis, Lisa M., Young, Robert J., Berger, Michael F., Mellinghoff, Ingo K.
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	London Nature Publishing Group UK 01.01.2019 Nature Publishing Group
Témata:	631/1647/2217 631/67/1922 Adults Analysis Biopsy Blood circulation Brain Brain cancer Brain tumors Cancer therapies Cerebrospinal fluid Chemotherapy Chromosome deletion Consortia Deoxyribonucleic acid Development and progression Diagnosis DNA Evolution Evolution, Molecular Gene deletion Genes, Neoplasm - genetics Genome, Human - genetics Genomes Genomics Genotypes Genotyping Glioblastoma - cerebrospinal fluid Glioblastoma - genetics Glioblastoma - pathology Glioma Glioma - cerebrospinal fluid Glioma - genetics Glioma - pathology Gliomas Growth factors Humanities and Social Sciences Humans Isocitrate dehydrogenase Letter Liquid Biopsy Methods Morbidity multidisciplinary Mutation Neoplasm Grading Oncology Patients Science Science (multidisciplinary) Signal transduction Signs and symptoms Surgery Telomerase Tumorigenesis Tumors United States
ISSN:	0028-0836, 1476-4687, 1476-4687
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Shrnutí:	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. Identification and sequencing of circulating tumour DNA in the cerebrospinal fluid of patients with glioma.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Present address: Medical Genetics and Human Genomics, Department of Pediatrics, Northwell Health; 350 Community Dr.; Suite 2133A; Manhasset, NY 11030. AUTHOR CONTRIBUTIONS AUTHOR INFORMATION Reprints and permissions information is available at www.nature.com/reprints. EIP reports advisory roles with AstraZeneca. VT is a founding investigator of Blue Rock Therapeutics. KSP reports stock ownership in Pfizer. LMD reports advisory roles for Sapience Therapeutics, Tocagen, BTG International, Roche, and Syndax. RJY reports research funding from Agios and advisory roles with Icon plc, NordicNeuroLab, and Puma Biotechnology. MFB reports advisory roles with Roche and research funding from Illumina. IKM reports research funding from General Electric, Amgen, and Lilly; advisory roles with Agios, Puma Biotechnology, and Debiopharm Group; and honoraria from Roche for a presentation. Correspondence and requests for materials should be addressed to bergerm1@mskcc.org and mellingi@mskcc.org. AMM, RHS, and EIP contributed equally to this work. AMM, RHS, EIP, LMD, RJY, MFB and IKM conceived and designed the study. AMM, RHS, EIP, RJY, MFB and IKM collected and assembled the data. AMM, RHS, EIP, MP, SB, ND, AS, SDS, LL, FM, XJ, CG, AV, MMS, VT, CWB, MR, RJY, MFB and IKM were responsible for provision of the study materials and the patients. AMM, RHS, EIP, YZ, AR, KP, RJY, MFB, IKM analyzed and interpreted the data. MP, CC, SAM, AS, FM processed the CSF and blood samples. AMM, RHS, EIP, W-YH, TAB, AV, LMD, KP, RJY, MFB, IKM provided administrative, material and technical support. AMM, RHS, EIP, DWT, CG, LMD, KP, RJY, MFB, IKM wrote the manuscript. All authors approved the manuscript.
ISSN:	0028-0836 1476-4687 1476-4687
DOI:	10.1038/s41586-019-0882-3