Abstract 4397: Deciphering the diversity of somatic alterations and Salmonella infection in gallbladder cancer by whole exome sequencing

Abstract

Abstract Background: Gallbladder cancer is fifth most common cancers among the gastrointestinal cancers with the majority of patients presented at an advanced state of the disease. In India, gallbladder cancer is a major problem in the northern part of the country with its highest incidence of 22/1,00,000 women and risk factors ranging from gallstones, female gender, ethnicity, Salmonella infections and genetic alterations. Despite its high incidence in our country, there is only few candidate gene based studies and systematic genome-wide studies are far in dismal. Hence there is an unmet need to understand the genomic landscape of Indian gallbladder cancer genome. Materials and methods: We interrogated the coding region of gallbladder cancer genome of 27 samples (10 paired and 7 unpaired tumors) using whole exome sequencing at an average coverage of 100X and above. Further, we validated our findings from whole exome sequencing in an extended cohort of 27 FFPE (Formalin fixed paraffin embedded) samples using other sequencing technologies. In addition we used a computational subtraction tool to identify Salmonella DNA sequences in the whole exome sequencing data. Results: We identified 383 somatic alterations across 17 tumors, which includes an average 112 synonymous, 245 missense, 8 nonsense, 8 indels and 8 splice site changes. The average mutation rate considering the paired tumors is about 14 mutations/Mb. We found recurrent alterations in TP53, CTNNB1, SF3B1, ATM, AKAP11 and other genes by exome sequencing analysis. In addition, we examined our exome sequencing data for identifying Salmonella sequences as well as presence of 143 HPV types using computational subtraction based on HPVDetector. In our analysis we found association of typhoidal Salmonella strains in 11 of 26 gall bladder cancer samples and non-typhoidal Salmonella species in 12 of 26 sample, 6 samples were co-infected with both. Moreover, we observed co-occurrence of TP53 alterations in 4 of 16 Salmonella positive samples while we did not observe TP53 alterations in Salmonella negative samples. Conclusion: Taken together, we present the landscape of somatic alterations in Indian gallbladder cancer genome and identification of non-typhoidal Salmonella species along with co- occurrence of TP53 alterations could aid in the treatment of gallbladder cancer. Note: This abstract was not presented at the meeting. Citation Format: Prajish Sundaram Iyer, Nilesh laxman Gardi, Malika Ranjan, Bikram Sahoo, Pratik Chandrani, Pawan Upadhyay, Mukta R. Ramadwar, Shailesh V. Shrikhande, Amit Dutt. Deciphering the diversity of somatic alterations and Salmonella infection in gallbladder cancer by whole exome sequencing [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4397. doi:10.1158/1538-7445.AM2017-4397