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Dziubańska-Kusibab, Paulina J; Berger, Hilmar; Battistini, Federica; Bouwman, Britta A M; Iftekhar, Amina; Katainen, Riku; Cajuso, Tatiana; Crosetto, Nicola; Orozco, Modesto; Aaltonen, Lauri A; Meyer, Thomas F
Nature medicine, 07/2020, Letnik: 26, Številka: 7Journal Article
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 associated with certain strains of Escherichia coli , 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 . The present study provides evidence for the etiological role of colibactin in human cancer.
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in: SICRIS
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