Characterization of colibactin-associated mutational signature in an Asian oral squamous cell carcinoma and in other mucosal tumor types
Characterization of colibactin-associated mutational signature in an Asian oral squamous cell carcinoma and in other mucosal tumor types
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DOI：
10.1101/gr.255620.119
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发表时间：
2020-06-01
期刊：
影响因子：
7
通讯作者：
Rozen, Steven G.
中科院分区：
文献类型：
--
作者：
Boot, Arnoud;Ng, Alvin W. T.;Rozen, Steven G.
突变特征可以揭示细胞在肿瘤形成之前和期间所暴露的突变过程的历史。我们预计，尚未发现的突变过程将进一步揭示导致癌症发生的突变。考虑到这一点，我们分析了36例亚洲口腔鳞状细胞癌的突变谱。来自口腔细菌感染患者的两个样本的突变光谱显示了新的突变特征。其中一个新的特征，SBS_A(N)T，其特征是胸腺嘧啶突变占优势，强烈的转录链偏向，以及在突变位点的4bp5‘端富集腺嘌呤。这份手稿中描述的突变特征被证明是由大肠杆菌产生的一种携带PKS-岛的细菌诱变剂Colibactin引起的。对公开的测序数据的检查显示，在来自几种粘膜组织类型的25个肿瘤中发现了SBS_A(N)T，扩大了观察到这种突变特征的组织列表。
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.