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Cerebrospinal fluid cfDNA sequencing for classification of central nervous system glioma

Primary central nervous system (CNS) gliomas can be classified by characteristic genetic alterations. In addition to solid tissue obtained via surgery or biopsy, cell-free DNA (cfDNA) from cerebrospinal fluid (CSF) is an alternative source of material for genomic analyses.We performed targeted next-...

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Main Authors: Iser, Florian (Author) , Hinz, Felix (Author) , Hoffmann, Dirk C. (Author) , Graßl, Niklas (Author) , Güngoör, Cansu (Author) , Meyer, Jochen (Author) , Dörner, Laura (Author) , Hofmann, Lea (Author) , Kelbch, Vanessa (Author) , Göbel, Kirsten (Author) , Mahmutoglu, Mustafa A. (Author) , Vollmuth, Philipp (Author) , Patel, Areeba (Author) , Nguyen, Duy (Author) , Kaulen, Leon D. (Author) , Mildenberger, Iris (Author) , Sahm, Katharina (Author) , Maaß, Kendra K. (Author) , Pajtler, Kristian Wilfried (Author) , Shankar, Ganesh M. (Author) , Weiler, Markus (Author) , Wildemann, Brigitte (Author) , Winkler, Frank (Author) , Deimling, Andreas von (Author) , Platten, Michael (Author) , Wick, Wolfgang (Author) , Sahm, Felix (Author) , Keßler, Tobias (Author)
Format: Article (Journal)
Language:English
Published: July 15 2024
In: Clinical cancer research
Year: 2024, Volume: 30, Issue: 14, Pages: 2974-2985
ISSN:1557-3265
DOI:10.1158/1078-0432.CCR-23-2907
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1158/1078-0432.CCR-23-2907
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Author Notes:Florian Iser, Felix Hinz, Dirk C. Hoffmann, Niklas Grassl, Cansu Güngoör, Jochen Meyer, Laura Dörner, Lea Hofmann, Vanessa Kelbch, Kirsten Göbel, Mustafa Ahmed Mahmutoglu, Philipp Vollmuth, Areeba Patel, Duy Nguyen, Leon D. Kaulen, Iris Mildenberger, Katharina Sahm, Kendra Maaß, Kristian W. Pajtler, Ganesh M. Shankar, Markus Weiler, Brigitte Wildemann, Frank Winkler, Andreas von Deimling, Michael Platten, Wolfgang Wick, Felix Sahm, and Tobias Kessler
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Summary:Primary central nervous system (CNS) gliomas can be classified by characteristic genetic alterations. In addition to solid tissue obtained via surgery or biopsy, cell-free DNA (cfDNA) from cerebrospinal fluid (CSF) is an alternative source of material for genomic analyses.We performed targeted next-generation sequencing of CSF cfDNA in a representative cohort of 85 patients presenting at two neurooncological centers with suspicion of primary or recurrent glioma. Copy-number variation (CNV) profiles, single-nucleotide variants (SNV), and small insertions/deletions (indel) were combined into a molecular-guided tumor classification. Comparison with the solid tumor was performed for 38 cases with matching solid tissue available.Cases were stratified into four groups: glioblastoma (n = 32), other glioma (n = 19), nonmalignant (n = 17), and nondiagnostic (n = 17). We introduced a molecular-guided tumor classification, which enabled identification of tumor entities and/or cancer-specific alterations in 75.0% (n = 24) of glioblastoma and 52.6% (n = 10) of other glioma cases. The overlap between CSF and matching solid tissue was highest for CNVs (26%-48%) and SNVs at predefined gene loci (44%), followed by SNVs/indels identified via uninformed variant calling (8%-14%). A molecular-guided tumor classification was possible for 23.5% (n = 4) of nondiagnostic cases.We developed a targeted sequencing workflow for CSF cfDNA as well as a strategy for interpretation and reporting of sequencing results based on a molecular-guided tumor classification in glioma.See related commentary by Abdullah, p. 2860
Item Description:Gesehen am 13.01.2025
Physical Description:Online Resource
ISSN:1557-3265
DOI:10.1158/1078-0432.CCR-23-2907

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