Tracking tumour evolution in glioma through liquid biopsies of cerebrospinal fluid.

TitleTracking tumour evolution in glioma through liquid biopsies of cerebrospinal fluid.
Publication TypeJournal Article
Year of Publication2019
AuthorsMiller AM, Shah RH, Pentsova EI, Pourmaleki M, Briggs S, Distefano N, Zheng Y, Skakodub A, Mehta SA, Campos C, Hsieh W-Y, S Selcuklu D, Ling L, Meng F, Jing X, Samoila A, Bale TA, W Y Tsui D, Grommes C, Viale A, Souweidane MM, Tabar V, Brennan CW, Reiner AS, Rosenblum M, Panageas KS, DeAngelis LM, Young RJ, Berger MF, Mellinghoff IK
Date Published2019 01
KeywordsEvolution, Molecular, Genes, Neoplasm, Genome, Human, Genomics, Glioblastoma, Glioma, Humans, Liquid Biopsy, Mutation, Neoplasm Grading

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

Alternate JournalNature
PubMed ID30675060
PubMed Central IDPMC6457907
Grant ListP30 CA008748 / CA / NCI NIH HHS / United States
P50 CA092629 / CA / NCI NIH HHS / United States
R35 NS105109 / NS / NINDS NIH HHS / United States
1 R35 NS105109 01 / NH / NIH HHS / United States