Colibactin mutational signatures in NTHL1 tumor syndrome and MUTYH associated polyposis patients.
Genes Chromosomes Cancer
; 63(1): e23208, 2024 Jan.
Article
in En
| MEDLINE
| ID: mdl-37795928
ABSTRACT
Polyketide synthase (pks) island harboring Escherichia coli are, under the right circumstances, able to produce the genotoxin colibactin. Colibactin is a risk factor for the development of colorectal cancer and associated with mutational signatures SBS88 and ID18. This study explores colibactin-associated mutational signatures in biallelic NTHL1 and MUTYH patients. Targeted Next Generation Sequencing (NGS) was performed on colorectal adenomas and carcinomas of one biallelic NTHL and 12 biallelic MUTYH patients. Additional fecal metagenomics and genome sequencing followed by mutational signature analysis was conducted for the NTHL1 patient. Targeted NGS of the NTHL1 patient showed somatic APC variants fitting SBS88 which was confirmed using WGS. Furthermore, fecal metagenomics revealed pks genes. Also, in 1 out of 11 MUTYH patient a somatic variant was detected fitting SBS88. This report shows that colibactin may influence development of colorectal neoplasms in predisposed patients.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Colorectal Neoplasms
/
Adenomatous Polyposis Coli
Type of study:
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
Genes Chromosomes Cancer
Journal subject:
BIOLOGIA MOLECULAR
/
NEOPLASIAS
Year:
2024
Type:
Article
Affiliation country:
Netherlands