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Colibactin DNA-damage signature indicates mutational impact in colorectal cancer
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Journal Article
Colibactin DNA-damage signature indicates mutational impact in colorectal cancer
2020
Overview
The mucosal epithelium is a common target of damage by chronic bacterial infections and the accompanying toxins, and most cancers originate from this tissue. We investigated whether colibactin, a potent genotoxin
1
associated with certain strains of
Escherichia coli
2
, creates a specific DNA-damage signature in infected human colorectal cells. Notably, the genomic contexts of colibactin-induced DNA double-strand breaks were enriched for an AT-rich hexameric sequence motif, associated with distinct DNA-shape characteristics. A survey of somatic mutations at colibactin target sites of several thousand cancer genomes revealed notable enrichment of this motif in colorectal cancers. Moreover, the exact double-strand-break loci corresponded with mutational hot spots in cancer genomes, reminiscent of a trinucleotide signature previously identified in healthy colorectal epithelial cells
3
. The present study provides evidence for the etiological role of colibactin in human cancer.
Identification of a DNA-damage signature induced by colibactin, a toxin expressed by some strains of
Escherichia coli
, is enriched in human colorectal cancers.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ Biomedical and Life Sciences
/ Cancer
/ Cell Proliferation - drug effects
/ Colorectal Neoplasms - genetics
/ Colorectal Neoplasms - microbiology
/ Colorectal Neoplasms - pathology
/ DNA
/ DNA Breaks, Double-Stranded - drug effects
/ E coli
/ Epithelial Cells - drug effects
/ Escherichia coli - pathogenicity
/ Etiology
/ Genomes
/ Humans
/ Letter
/ Mucosa
/ Mutation
/ Nucleotide Motifs - drug effects
/ Toxins
