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Identification of novel mutational signatures in Asian oral squamous cell carcinomas associated with bacterial infections

By Arnoud Boot, Alvin W.T. Ng, Fui Teen Chong, Szu-Chi Ho, Willie Yu, Daniel S.W. Tan, N. Gopalakrishna Iyer, Steven G. Rozen

Posted 19 Jul 2018
bioRxiv DOI: 10.1101/368753

Mutational signatures can reveal the history of mutagenic processes that cells were exposed to prior to and during tumourigenesis. 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, both 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 striking enrichment for adenines in the 4 base pairs 5′ of mutation sites. Examination of publicly available sequencing data revealed SBS_AnT in 23 tumours from several tissue types, all of which mucosal tissues host to human symbionts or in direct contact with tissues that host human symbionts. This is the first report of mutagenesis associated with bacterial infection in cancer.

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