| Title: |
Detection of Neoplasms by Metagenomic Next-Generation Sequencing of Cerebrospinal Fluid |
| Authors: |
Gu, Wei; Rauschecker, Andreas M; Hsu, Elaine; Zorn, Kelsey C; Sucu, Yasemin; Federman, Scot; Gopez, Allan; Arevalo, Shaun; Sample, Hannah A; Talevich, Eric; Nguyen, Eric D; Gottschall, Marc; Nourbakhsh, Bardia; Gold, Carl A; Cree, Bruce AC; Douglas, Vanja C; Richie, Megan B; Shah, Maulik P; Josephson, S Andrew; Gelfand, Jeffrey M; Miller, Steve; Wang, Linlin; Tihan, Tarik; DeRisi, Joseph L; Chiu, Charles Y; Wilson, Michael R |
| Source: |
JAMA Neurology, vol 78, iss 11 |
| Publisher Information: |
eScholarship, University of California |
| Publication Year: |
2021 |
| Collection: |
University of California: eScholarship |
| Subject Terms: |
32 Biomedical and Clinical Sciences (for-2020); 3202 Clinical Sciences (for-2020); Cancer (rcdc); Brain Disorders (rcdc); Clinical Research (rcdc); Neurosciences (rcdc); Rare Diseases (rcdc); 2.1 Biological and endogenous factors (hrcs-rac); 4.2 Evaluation of markers and technologies (hrcs-rac); Neurological (hrcs-hc); 3 Good Health and Well Being (sdg); Adult (mesh); Aged (mesh); Biomarkers; Tumor (mesh); Case-Control Studies (mesh); Central Nervous System Neoplasms (mesh); Female (mesh); High-Throughput Nucleotide Sequencing (mesh); Humans (mesh); Male (mesh); Metagenomics (mesh); Middle Aged (mesh); Sensitivity and Specificity (mesh); Sequence Analysis; DNA (mesh) |
| Time: |
1355 - 1366 |
| Description: |
Importance: Cerebrospinal fluid (CSF) cytologic testing and flow cytometry are insensitive for diagnosing neoplasms of the central nervous system (CNS). Such clinical phenotypes can mimic infectious and autoimmune causes of meningoencephalitis. Objective: To ascertain whether CSF metagenomic next-generation sequencing (mNGS) can identify aneuploidy, a hallmark of malignant neoplasms, in difficult-to-diagnose cases of CNS malignant neoplasm. Design, Setting, and Participants: Two case-control studies were performed at the University of California, San Francisco (UCSF). The first study used CSF specimens collected at the UCSF Clinical Laboratories between July 1, 2017, and December 31, 2019, and evaluated test performance in specimens from patients with a CNS malignant neoplasm (positive controls) or without (negative controls). The results were compared with those from CSF cytologic testing and/or flow cytometry. The second study evaluated patients who were enrolled in an ongoing prospective study between April 1, 2014, and July 31, 2019, with presentations that were suggestive of neuroinflammatory disease but who were ultimately diagnosed with a CNS malignant neoplasm. Cases of individuals whose tumors could have been detected earlier without additional invasive testing are discussed. Main Outcomes and Measures: The primary outcome measures were the sensitivity and specificity of aneuploidy detection by CSF mNGS. Secondary subset analyses included a comparison of CSF and tumor tissue chromosomal abnormalities and the identification of neuroimaging characteristics that were associated with test performance. Results: Across both studies, 130 participants were included (median [interquartile range] age, 57.5 [43.3-68.0] years; 72 men [55.4%]). The test performance study used 125 residual laboratory CSF specimens from 47 patients with a CNS malignant neoplasm and 56 patients with other neurological diseases. The neuroinflammatory disease study enrolled 12 patients and 17 matched control participants. The sensitivity ... |
| Document Type: |
article in journal/newspaper |
| Language: |
unknown |
| Relation: |
qt3bf3r4dk; https://escholarship.org/uc/item/3bf3r4dk |
| DOI: |
10.1001/jamaneurol.2021.3088 |
| Availability: |
https://escholarship.org/uc/item/3bf3r4dk; https://doi.org/10.1001/jamaneurol.2021.3088 |
| Rights: |
public |
| Accession Number: |
edsbas.34147288 |
| Database: |
BASE |