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Characterization of colibactin-associated mutational signature in an Asian oral squamous cell carcinoma and in other mucosal tumor types

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 spec...

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Detalles Bibliográficos
Autores principales: Boot, Arnoud, Ng, Alvin W.T., Chong, Fui Teen, Ho, Szu-Chi, Yu, Willie, Tan, Daniel S.W., Iyer, N. Gopalakrishna, Rozen, Steven G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7370881/
https://www.ncbi.nlm.nih.gov/pubmed/32661091
http://dx.doi.org/10.1101/gr.255620.119
Descripción
Sumario: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_A(n)T, 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_A(n)T in 25 tumors from several mucosal tissue types, expanding the list of tissues in which this mutational signature is observed.