Cell-free chromatin immunoprecipitation can determine tumor gene expression in lung cancer patients.
cell-free ChIP
epigenetics
gene expression
liquid biopsy
non-small-cell lung cancer
small-cell lung cancer
Journal
Molecular oncology
ISSN: 1878-0261
Titre abrégé: Mol Oncol
Pays: United States
ID NLM: 101308230
Informations de publication
Date de publication:
05 2023
05 2023
Historique:
revised:
03
01
2023
received:
17
11
2022
accepted:
09
02
2023
medline:
8
5
2023
pubmed:
25
2
2023
entrez:
24
2
2023
Statut:
ppublish
Résumé
Cell-free DNA (cfDNA) in blood plasma can be bound to nucleosomes that contain post-translational modifications representing the epigenetic profile of the cell of origin. This includes histone H3 lysine 36 trimethylation (H3K36me3), a marker of active transcription. We hypothesised that cell-free chromatin immunoprecipitation (cfChIP) of H3K36me3-modified nucleosomes present in blood plasma can delineate tumour gene expression levels. H3K36me3 cfChIP followed by targeted NGS (cfChIP-seq) was performed on blood plasma samples from non-small-cell lung cancer (NSCLC) patients (NSCLC, n = 8), small-cell lung cancer (SCLC) patients (SCLC, n = 4) and healthy controls (n = 4). H3K36me3 cfChIP-seq demonstrated increased enrichment of mutated alleles compared with normal alleles in plasma from patients with known somatic cancer mutations. Additionally, genes identified to be differentially expressed in SCLC and NSCLC tumours had concordant H3K36me3 cfChIP enrichment profiles in NSCLC (sensitivity = 0.80) and SCLC blood plasma (sensitivity = 0.86). Findings here expand the utility of cfDNA in liquid biopsies to characterise treatment resistance, cancer subtyping and disease progression.
Identifiants
pubmed: 36825535
doi: 10.1002/1878-0261.13394
pmc: PMC10158780
doi:
Substances chimiques
Nucleosomes
0
Cell-Free Nucleic Acids
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
722-736Informations de copyright
© 2023 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
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