Home > Publications database > Improved detection of colibactin-induced mutations by genotoxic E. coli in organoids and colorectal cancer. > print

001     288881
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024 7 _ |a 10.1016/j.ccell.2024.02.009
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024 7 _ |a 1535-6108
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041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Rosendahl Huber, Axel
|b 0
245 _ _ |a Improved detection of colibactin-induced mutations by genotoxic E. coli in organoids and colorectal cancer.
260 _ _ |a New York, NY
|c 2024
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336 7 _ |a article
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520 _ _ |a Co-culture of intestinal organoids with a colibactin-producing pks+E. coli strain (EcC) revealed mutational signatures also found in colorectal cancer (CRC). E. coli Nissle 1917 (EcN) remains a commonly used probiotic, despite harboring the pks operon and inducing double strand DNA breaks. We determine the mutagenicity of EcN and three CRC-derived pks+E. coli strains with an analytical framework based on sequence characteristic of colibactin-induced mutations. All strains, including EcN, display varying levels of mutagenic activity. Furthermore, a machine learning approach attributing individual mutations to colibactin reveals that patients with colibactin-induced mutations are diagnosed at a younger age and that colibactin can induce a specific APC mutation. These approaches allow the sensitive detection of colibactin-induced mutations in ∼12% of CRC genomes and even in whole exome sequencing data, representing a crucial step toward pinpointing the mutagenic activity of distinct pks+E. coli strains.
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650 _ 7 |a bacteria
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650 _ 7 |a cancer genomics
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650 _ 7 |a colibactin
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650 _ 7 |a colorectal cancer
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650 _ 7 |a genotoxins
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650 _ 7 |a machine learning
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650 _ 7 |a mutagenesis
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650 _ 7 |a mutational signatures
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650 _ 7 |a organoids
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650 _ 7 |a probiotics
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700 1 _ |a Pleguezuelos-Manzano, Cayetano
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700 1 _ |a Puschhof, Jens
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700 1 _ |a Ubels, Joske
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700 1 _ |a Boot, Charelle
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700 1 _ |a Saftien, Aurelia
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700 1 _ |a Verheul, Mark
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700 1 _ |a Trabut, Laurianne T
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700 1 _ |a Groenen, Niels
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700 1 _ |a van Roosmalen, Markus
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700 1 _ |a Ouyang, Kyanna S
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700 1 _ |a Wood, Henry
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700 1 _ |a Quirke, Phil
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700 1 _ |a Meijer, Gerrit
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700 1 _ |a Cuppen, Edwin
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700 1 _ |a Clevers, Hans
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700 1 _ |a van Boxtel, Ruben
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773 _ _ |a 10.1016/j.ccell.2024.02.009
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856 4 _ |u https://inrepo02.dkfz.de/record/288881/files/1-s2.0-S1535610824000539-main.pdf
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