Cerebrospinal Fluid cfDNA Sequencing for Classification of Central Nervous System Glioma.
Clin Cancer Res
; 30(14): 2974-2985, 2024 Jul 15.
Article
em En
| MEDLINE
| ID: mdl-38295147
ABSTRACT
PURPOSE:
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. EXPERIMENTALDESIGN:
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.RESULTS:
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.CONCLUSIONS:
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Biomarcadores Tumorais
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Variações do Número de Cópias de DNA
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Sequenciamento de Nucleotídeos em Larga Escala
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Ácidos Nucleicos Livres
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Glioma
Tipo de estudo:
Prognostic_studies
Limite:
Adult
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Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article