ChIP-seq Analysis to Explore DNA Replication Profile in Trifluridine-treated Human Colorectal Cancer Cells
ChIP-seq
Trifluridine
colorectal cancer
trifluridine/tipiracil (TAS-102)
Journal
Anticancer research
ISSN: 1791-7530
Titre abrégé: Anticancer Res
Pays: Greece
ID NLM: 8102988
Informations de publication
Date de publication:
Jul 2019
Jul 2019
Historique:
received:
18
02
2019
revised:
23
03
2019
accepted:
26
03
2019
entrez:
3
7
2019
pubmed:
3
7
2019
medline:
10
7
2019
Statut:
ppublish
Résumé
Trifluridine (FTD) is a key component of the novel oral antitumor drug trifluridine/tipiracil that has been approved for the treatment of metastatic colorectal cancer. In this study, a comprehensive analysis of DNA replication profile in FTD-treated colon cancer cells was performed. HCT-116 cells were exposed to BrdU or FTD and subjected to DNA immunoprecipitation. Immunoprecipitated DNA was sequenced; the density of aligned reads along the genome was calculated. Peak finding, gene ontology, and motif analysis were performed using MACS, GREAT, and MEME, respectively. We identified 6,043 and 5,080 high-confidence FTD and BrdU peaks in HCT-116 cells, respectively. Of 6,043 FTD peaks, 2,911 peaks were uncommon to BrdU. We observed that FTD was preferentially incorporated into genomic regions containing simple repeats, CpG islands, and gene bodies. Conserved motifs in FTD peaks contained dinucleotide repeats such as (GT)n. Global FTD incorporation patterns delineated FTD, preferentially incorporating loci in cancer cells.
Sections du résumé
BACKGROUND/AIM
OBJECTIVE
Trifluridine (FTD) is a key component of the novel oral antitumor drug trifluridine/tipiracil that has been approved for the treatment of metastatic colorectal cancer. In this study, a comprehensive analysis of DNA replication profile in FTD-treated colon cancer cells was performed.
MATERIALS AND METHODS
METHODS
HCT-116 cells were exposed to BrdU or FTD and subjected to DNA immunoprecipitation. Immunoprecipitated DNA was sequenced; the density of aligned reads along the genome was calculated. Peak finding, gene ontology, and motif analysis were performed using MACS, GREAT, and MEME, respectively.
RESULTS
RESULTS
We identified 6,043 and 5,080 high-confidence FTD and BrdU peaks in HCT-116 cells, respectively. Of 6,043 FTD peaks, 2,911 peaks were uncommon to BrdU. We observed that FTD was preferentially incorporated into genomic regions containing simple repeats, CpG islands, and gene bodies. Conserved motifs in FTD peaks contained dinucleotide repeats such as (GT)n.
CONCLUSION
CONCLUSIONS
Global FTD incorporation patterns delineated FTD, preferentially incorporating loci in cancer cells.
Identifiants
pubmed: 31262880
pii: 39/7/3565
doi: 10.21873/anticanres.13502
doi:
Substances chimiques
Antimetabolites, Antineoplastic
0
Bromodeoxyuridine
G34N38R2N1
Trifluridine
RMW9V5RW38
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
3565-3570Informations de copyright
Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.