Enrichment of colibactin-associated mutational signatures in unexplained colorectal polyposis patients.
BMC Cancer
; 24(1): 104, 2024 Jan 18.
Article
en En
| MEDLINE
| ID: mdl-38238650
ABSTRACT
BACKGROUND:
Colibactin, a genotoxin produced by polyketide synthase harboring (pks+) bacteria, induces double-strand breaks and chromosome aberrations. Consequently, enrichment of pks+Escherichia coli in colorectal cancer and polyposis suggests a possible carcinogenic effect in the large intestine. Additionally, specific colibactin-associated mutational signatures; SBS88 and ID18 in the Catalogue of Somatic Mutations in Cancer database, are detected in colorectal carcinomas. Previous research showed that a recurrent APC splice variant perfectly fits SBS88.METHODS:
In this study, we explore the presence of colibactin-associated signatures and fecal pks in an unexplained polyposis cohort. Somatic targeted Next-Generation Sequencing (NGS) was performed for 379 patients. Additionally, for a subset of 29 patients, metagenomics was performed on feces and mutational signature analyses using Whole-Genome Sequencing (WGS) on Formalin-Fixed Paraffin Embedded (FFPE) colorectal tissue blocks.RESULTS:
NGS showed somatic APC variants fitting SBS88 or ID18 in at least one colorectal adenoma or carcinoma in 29% of patients. Fecal metagenomic analyses revealed enriched presence of pks genes in patients with somatic variants fitting colibactin-associated signatures compared to patients without variants fitting colibactin-associated signatures. Also, mutational signature analyses showed enrichment of SBS88 and ID18 in patients with variants fitting these signatures in NGS compared to patients without.CONCLUSIONS:
These findings further support colibactins ability to mutagenize colorectal mucosa and contribute to the development of colorectal adenomas and carcinomas explaining a relevant part of patients with unexplained polyposis.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Carcinoma
/
Neoplasias Colorrectales
/
Adenoma
/
Policétidos
Tipo de estudio:
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
BMC Cancer
Asunto de la revista:
NEOPLASIAS
Año:
2024
Tipo del documento:
Article
País de afiliación:
Países Bajos