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Colibactin DNA-damage signature indicates mutational impact in colorectal cancer.

Authors :
Dziubańska-Kusibab PJ
Berger H
Battistini F
Bouwman BAM
Iftekhar A
Katainen R
Cajuso T
Crosetto N
Orozco M
Aaltonen LA
Meyer TF
Source :
Nature medicine [Nat Med] 2020 Jul; Vol. 26 (7), pp. 1063-1069. Date of Electronic Publication: 2020 Jun 01.
Publication Year :
2020

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 <superscript>1</superscript> associated with certain strains of Escherichia coli <superscript>2</superscript> , 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 <superscript>3</superscript> . The present study provides evidence for the etiological role of colibactin in human cancer.

Details

Language :
English
ISSN :
1546-170X
Volume :
26
Issue :
7
Database :
MEDLINE
Journal :
Nature medicine
Publication Type :
Academic Journal
Accession number :
32483361
Full Text :
https://doi.org/10.1038/s41591-020-0908-2