Mutational signature in colorectal cancer induced by genotoxic pks+ E. coli

Study ID Alternative Stable ID Type
EGAS00001003934 Other

Study Description

Various species of the intestinal microbiota have been associated with the development of colorectal cancer (CRC), yet a direct role of bacteria in the occurrence of oncogenic mutations has not been established. Escherichia coli can carry the pathogenicity island pks, which encodes a set of enzymes that synthesize colibactin. This compound is believed to alkylate DNA on adenine residues and induces double strand breaks in cultured cells. Here, we expose human intestinal organoids to genotoxic pks+ Escherichia coli by repeated luminal injection over a period of 5 months. Whole genome sequencing of clonal organoids before and after this exposure reveals a distinct mutational signature, absent from organoids injected with isogenic pks-mutant bacteria. The same mutational signature is detected in a subset of 5876 human cancer genomes from two independent cohorts, predominantly in CRC. Our study describes a distinct mutational signature in CRC and implies that the underlying mutational process directly results from past exposure to bacteria carrying the colibactin-producing pks ... (Show More)

Study Datasets 1 dataset.

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Dataset ID Description Technology Samples
Organoid cultures were exposed to two different E.Coli strains and a dye control with three biological duplicates. Their original culture was harvested as a control. In total 10 organoid cultures were whole-genome sequenced using the Novaseq6000 platforms. The data is deposited as .bam format.
Illumina NovaSeq 6000 20

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