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.

Chen, B., Ramazzotti, D., Heide, T., Spiteri, I., Fernandez-Mateos, J., James, C., et al. (2023). Contribution of pks+ E. coli mutations to colorectal carcinogenesis. NATURE COMMUNICATIONS, 14(1) [10.1038/s41467-023-43329-5].

Contribution of pks+ E. coli mutations to colorectal carcinogenesis

Ramazzotti, D;
2023

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.
Articolo in rivista - Articolo scientifico
Colorectal cancer; Mutational signatures; Tumorigenesis
English
29-nov-2023
2023
14
1
7827
open
Chen, B., Ramazzotti, D., Heide, T., Spiteri, I., Fernandez-Mateos, J., James, C., et al. (2023). Contribution of pks+ E. coli mutations to colorectal carcinogenesis. NATURE COMMUNICATIONS, 14(1) [10.1038/s41467-023-43329-5].
File in questo prodotto:
File Dimensione Formato  
Chen-2023-Nat Communicat-VoR.pdf

accesso aperto

Descrizione: Article
Tipologia di allegato: Publisher’s Version (Version of Record, VoR)
Licenza: Creative Commons
Dimensione 2.51 MB
Formato Adobe PDF
2.51 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/452178
Citazioni
  • Scopus 1
  • ???jsp.display-item.citation.isi??? 0
Social impact