Journal Article

DKFZ-2024-00523

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Improved detection of colibactin-induced mutations by genotoxic E. coli in organoids and colorectal cancer.

Rosendahl Huber, A. ; Pleguezuelos-Manzano, C. ; Puschhof, J.DKFZ* ; Ubels, J. ; Boot, C. ; Saftien, A.DKFZ* ; Verheul, M. ; Trabut, L. T. ; Groenen, N. ; van Roosmalen, M. ; Ouyang, K. S.DKFZ* ; Wood, H. ; Quirke, P. ; Meijer, G. ; Cuppen, E. ; Clevers, H. ; van Boxtel, R.

2024
Elsevier New York, NY

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Please use a persistent id in citations: doi:10.1016/j.ccell.2024.02.009

Abstract: 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.

Keyword(s): bacteria ; cancer genomics ; colibactin ; colorectal cancer ; genotoxins ; machine learning ; mutagenesis ; mutational signatures ; organoids ; probiotics

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Contributing Institute(s):

1. Mikrobiom und Krebs (F220)
2. Mikrobiom und Krebs (D480)

Research Program(s):

1. 314 - Immunologie und Krebs (POF4-314) (POF4-314)

Appears in the scientific report 2024

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 50 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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