Cotinine_induced_lung_cancer_in_mice_
Our preliminary results shows that 15 and 20% of male mice fed with Cot (15 mg/ml) water for 13 and 16 months developed lung adenocarcinoma, respectively.  In the current proposal, 6-8 week old male mice will be exposed to cotinine for 13 months. Genomic DNA from 5 control mouse lungs and 30 cotinine lung tumors + 30 surrounding tissues will be extracted for whole genome exome sequencing.  Mutation signatures will be analyzed. Significantly mutated genes will be identified using the MutSig2CV algorithm and SigProfiler. Results will allow us to determine mutation signatures and whether the mutations are consistent with the types of DNA adduct induced by Cot (g-OH-PdG, which induces both G:C > T: A and G:C > A:T mutations, and O6-medG, which induces exclusively G:C > A:T mutations). Furthermore, we will attempt to identify cancer driver genes, which will enhance our understanding of the pathway by which Cotinine induces lung cancer.
Our preliminary results shows that 15 and 20% of male mice fed with Cot (15 mg/ml) water for 13 and 16 months developed lung adenocarcinoma, respectively.  In the current proposal, 6-8 week old male mice will be exposed to cotinine for 13 months. Genomic DNA from 5 control mouse lungs and 30 cotinine lung tumors + 30 surrounding tissues will be extracted for whole genome exome sequencing.  Mutation signatures will be analyzed. Significantly mutated genes will be identified using the MutSig2CV algorithm and SigProfiler. Results will allow us to determine mutation signatures and whether the mutations are consistent with the types of DNA adduct induced by Cot (g-OH-PdG, which induces both G:C > T: A and G:C > A:T mutations, and O6-medG, which induces exclusively G:C > A:T mutations). Furthermore, we will attempt to identify cancer driver genes, which will enhance our understanding of the pathway by which Cotinine induces lung cancer.