Low-coverage whole-genome sequencing of cerebrospinal-fluid-derived cell-free DNA in brain tumor patients

• Main Authors: Kumar, R. (Author), Liu, A.P.Y (Author), Northcott, P.A (Author), Robinson, G.W (Author), Smith, K.S (Author)
• Format: Article
• Language: English
• Published: Cell Press 2022
• Subjects: Bioinformatics; Cancer; Clinical Protocol; Genomics; Health Sciences; Molecular Biology; Neuroscience; Sequence analysis; Sequencing
• Online Access: View Fulltext in Publisher
• ISBN: 26661667 (ISSN)
• DOI: 10.1016/j.xpro.2022.101292

This protocol summarizes the pipeline for analysis of tumor-derived cell-free DNA (cfDNA) from cerebrospinal fluid (CSF) using low-coverage whole-genome sequencing (lcWGS). This approach enables resolution of chromosomal and focal copy-number variations (CNVs) as oncologic signatures, particularly for patients with central nervous system tumors. Our strategy tolerates sub-nanogram cfDNA input and is thus optimized for CSF samples where cfDNA yields are typically low. Overall, the detection of tumor-specific signatures in CSF-derived cfDNA is a promising biomarker for personalization of brain-tumor therapy. For complete details on the use and execution of this protocol, please refer to Liu et al. (2021). © 2022 The Author(s)