Colibactin DNA-damage signature indicates mutational impact in colorectal cancer

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Dziubanska-Kusibab , P J , Berger , H , Battistini , F , Bouwman , B A M , Iftekhar , A , Katainen , R , Cajuso , T , Crosetto , N , Orozco , M , Aaltonen , L A & Meyer , T F 2020 , ' Colibactin DNA-damage signature indicates mutational impact in colorectal cancer ' , Nature Medicine , vol. 26 , no. 7 , pp. 1063-+ .

Title: Colibactin DNA-damage signature indicates mutational impact in colorectal cancer
Author: Dziubanska-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.
Contributor organization: Lauri Antti Aaltonen / Principal Investigator
ATG - Applied Tumor Genomics
Research Programs Unit
Department of Medical and Clinical Genetics
University of Helsinki
Date: 2020-07
Language: eng
Number of pages: 25
Belongs to series: Nature Medicine
ISSN: 1078-8956
Abstract: 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.
3111 Biomedicine
1182 Biochemistry, cell and molecular biology
Peer reviewed: Yes
Rights: unspecified
Usage restriction: openAccess
Self-archived version: acceptedVersion

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