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Terlouw, D.; Boot, A.; Ducarmon, Q.R.; Nooij, S.; Jessurun, M.A.; Leerdam, M.E. van; ... ; Nielsen, M. (2023)

Colibactin mutational signatures in NTHL1 tumor syndrome and MUTYH associated polyposis patients

Article / Letter to editor
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...Show more 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.
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colibactin
hereditary colorectal cancer
mutational signatures
All authors
Terlouw, D.; Boot, A.; Ducarmon, Q.R.; Nooij, S.; Jessurun, M.A.; Leerdam, M.E. van; Tops, C.M.; Langers, A.M.J.; Morreau, H.; Wezel, T. van; Nielsen, M.
Date
2023-10-05
Journal
Genes, Chromosomes & Cancer
Volume
63
Issue
1
DOI
doi:10.1002/gcc.23208
Link
https://onlinelibrary.wiley.com/doi/10.1002/gcc.23208