We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Contribution of pks<sup>+</sup>E. coli mutations to colorectal carcinogenesis.
- Authors
Chen, Bingjie; Ramazzotti, Daniele; Heide, Timon; Spiteri, Inmaculada; Fernandez-Mateos, Javier; James, Chela; Magnani, Luca; Graham, Trevor A.; Sottoriva, Andrea
- Abstract
The dominant mutational signature in colorectal cancer genomes is C > T deamination (COSMIC Signature 1) and, in a small subgroup, mismatch repair signature (COSMIC signatures 6 and 44). Mutations in common colorectal cancer driver genes are often not consistent with those signatures. Here we perform whole-genome sequencing of normal colon crypts from cancer patients, matched to a previous multi-omic tumour dataset. We analyse normal crypts that were distant vs adjacent to the cancer. In contrast to healthy individuals, normal crypts of colon cancer patients have a high incidence of pks + (polyketide synthases) E.coli (Escherichia coli) mutational and indel signatures, and this is confirmed by metagenomics. These signatures are compatible with many clonal driver mutations detected in the corresponding cancer samples, including in chromatin modifier genes, supporting their role in early tumourigenesis. These results provide evidence that pks + E.coli is a potential driver of carcinogenesis in the human gut. Common driver mutations in colorectal cancer (CRC) are not always consistent with frequent mutational signatures. Here, the authors analyse spatially annotated colon crypts in CRC patients and find mutational signatures of pks+ E. coli that are consistent with driver mutations, suggesting a potential role of pks+ E. coli in carcinogenesis.
- Subjects
ESCHERICHIA coli; HUMAN carcinogenesis; POLYKETIDE synthases; COLON cancer; CANCER genes
- Publication
Nature Communications, 2023, Vol 14, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-023-43329-5