Colibactin DNA-damage signature indicates mutational impact in colorectal cancer
Menée sur des cellules colorectales humaines infectées par la bactérie Escherichia coli et menée à partir notamment de données du projet "The Cancer Genome Atlas", cette étude met en évidence des cassures double-brin de l'ADN associées à la colibactine, une toxine provenant de certaines souches d'Escherichia coli, et démontre le rôle de cette toxine dans la survenue de tumeurs
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 genotoxin1 associated with certain strains of Escherichia coli2, 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 cells3. The present study provides evidence for the etiological role of colibactin in human cancer.