Characterization of colibactin-associated mutational signature in an Asian oral squamous cell carcinoma and in other mucosal tumor types
Autor: | Fui Teen Chong, Alvin Wei Tian Ng, Szu-Chi Ho, Daniel Shao-Weng Tan, Willie Yu, N. Gopalakrishna Iyer, Arnoud Boot, Steven G. Rozen |
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Rok vydání: | 2020 |
Předmět: |
DNA Mutational Analysis
Cell Mutagenesis (molecular biology technique) Mutagen Biology medicine.disease_cause 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Asian People Colibactin Exome Sequencing Escherichia coli Genetics medicine Humans Basal cell Escherichia coli Infections Genetics (clinical) 030304 developmental biology 0303 health sciences Mutation Mucous Membrane Research Computational Biology DNA Thymine medicine.anatomical_structure chemistry Mutagenesis Polyketides Carcinoma Squamous Cell Mouth Neoplasms Peptides Carcinogenesis 030217 neurology & neurosurgery Mutagens |
Zdroj: | Genome Res |
ISSN: | 1549-5469 1088-9051 |
Popis: | Mutational signatures can reveal the history of mutagenic processes that cells were exposed to before and during tumorigenesis. We expect that as-yet-undiscovered mutational processes will shed further light on mutagenesis leading to carcinogenesis. With this in mind, we analyzed the mutational spectra of 36 Asian oral squamous cell carcinomas. The mutational spectra of two samples from patients who presented with oral bacterial infections showed novel mutational signatures. One of these novel signatures, SBS_AnT, is characterized by a preponderance of thymine mutations, strong transcriptional strand bias, and enrichment for adenines in the 4 bp 5′ of mutation sites. The mutational signature described in this manuscript was shown to be caused by colibactin, a bacterial mutagen produced by E. coli carrying the pks-island. Examination of publicly available sequencing data revealed SBS_AnT in 25 tumors from several mucosal tissue types, expanding the list of tissues in which this mutational signature is observed. |
Databáze: | OpenAIRE |
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