Transcriptome signatures of tobacco carcinogens hint the alteration of TAF6 as a specific feature in smokers lung cancer

Background: Sequencing studies of human lung adenocarcinoma(LUAD) and carcinogens induced LUAD in animal models showed how the different mutational processes leave their specific signatures in the genome. Despite the intense effort, those signatures were extracted from heterogeneous tumor tissues and underestimated the expressed single nucleotide variation (eSNV). Aim: To define transcriptome mutational signature in carcinogen-induced LUAD, we investigated the raised mutations in transcriptome of different carcinogen-induced LUAD cell lines and compared those signatures with LUAD samples. Method: We used urethane and diethylnitrosamine, tobacco carcinogens, to induce LUAD in different strains of inbred mice and established cell lines thereof(n = 13).we selected a collection of 16 human LUAD samples (8 smokers and 8never smokers). RNA was subjected to RNAseq. Data were analyzed for the detection of eSNV. Results: In 14550 eSNV, we observed 15 recurring eSNV across all LUAD cell lines. As for the cell lines, we retrieved the mutational spectrum across the transcriptomes of our human samples. To conclude our validation of the tobacco-carcinogens transcriptome signature, we compared the presence of those in the smoker and never-smoker samples. We identified TAF6 alteration to be present only in smokers. Conclusion: We predict that transcriptome based approach on the mutational signature of carcinogens-induced cell lines can be applied to define signatures of alteration scalable to human scenarios. Moreover, our study defined the alteration of a new oncosoppressor, TAF6, in the panorama of smokers lung adenocarcinoma that deserves further investigation.