Colibactin DNA-damage signature indicates mutational impact in colorectal cancer.
Nat Med
; 26(7): 1063-1069, 2020 07.
Article
en En
| MEDLINE
| ID: mdl-32483361
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 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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Péptidos
/
Daño del ADN
/
Neoplasias Colorrectales
/
Roturas del ADN de Doble Cadena
/
Policétidos
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Nat Med
Asunto de la revista:
BIOLOGIA MOLECULAR
/
MEDICINA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Alemania