Bacterial Dna Integrations In The Genomes Of Gastric Tumor And Adjacent Samples

Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LAThere are 10 times more bacterial cells in the human body than human cells, and various bacteria are known to influence carcinogenesis. While viral DNA integrations in the human genome have been shown to promote carcinogenesis, bacterial DNA integrations (BDI) into the human genome are rarely investigated. Our previous analysis of publicly available sequencing data from the Cancer Genome Atlas showed BDIs from Pseudomonas spp. rRNA into the 5’-UTR of four proto-oncogenes as well as in Ig (the immunoglobulin gene) of gastric cancer samples. However, we were left with many unanswered questions when we were unable to obtain the materials required to validate our findings. Therefore, we sought to sequence a different cohort of gastric cancer patients in order to identify BDIs. Whole exome sequencing was completed on seven tumor samples and six adjacent gastric samples, as well as one intestinal metaplasia sample and one non-atrophic gastritis sample. Four of those samples were also investigated with transcriptomics and whole genome sequencing. Using our previously published BWA-based pipeline, we identified putative BDIs from Helicobacter pylori rRNA into numerous genes in one tumor sample as well as in its adjacent matched sample, including BDIs in the Ig locus. Helicobacter pylori is considered a carcinogen by the World Health Organization due to its ability to promote carcinogenesis in gastric tissue, causing us to speculate that these integrations could be carcinogenic. Similarly to our analysis of the Cancer Genome Atlas data, we also identified a few samples with BDIs from Pseudomonas spp. and about half of the samples possessed BDIs from other bacteria. We identified at least one BDI in each sample regardless of the sequencing data type. Validation of these results is ongoing and will be presented. Given these results, more consideration should be given to BDIs into the human genome when bacterial associations with diseases are suspected.Citation Format: Kelly Robinson, Nikhil Kumar, Javier Torres, Julie C. Dunning Hotopp. Bacterial DNA integrations in the genomes of gastric tumor and adjacent samples. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3299.