An atlas of the tissue and blood metagenome in cancer reveals novel links between bacteria, viruses and cancer

Abstract

Abstract Background Host tissue infections by bacteria and viruses can cause cancer. Known viral carcinogenic mechanisms are disruption of the host genome via genomic integration and expression of oncogenic viral proteins. An important bacterial carcinogenic mechanism is chronic inflammation. Massively parallel sequencing now routinely generates datasets large enough to contain detectable traces of bacterial and viral nucleic acids of taxa that colonize the examined tissue or are integrated into the host genome. However, this hidden resource has not been comprehensively studied in large patient cohorts. Methods In the present study, 3025 whole genome sequencing datasets and, where available, corresponding RNA-seq datasets are leveraged to gain insight into novel links between viruses, bacteria, and cancer. Datasets were obtained from multiple International Cancer Genome Consortium studies, with additional controls added from the 1000 genome project. A customized pipeline based on KRAKEN was developed and validated to identify bacterial and viral sequences in the datasets. Raw results were stringently filtered to reduce false positives and remove likely contaminants. Results The resulting map confirms known links and expands current knowledge by identifying novel associations. Moreover, the detection of certain bacteria or viruses is associated with profound differences in patient and tumor phenotypes, such as patient age, tumor stage, survival, and somatic mutations in cancer genes or gene expression profiles. Conclusions Overall, these results provide a detailed, unprecedented map of links between viruses, bacteria, and cancer that can serve as a reference for future studies and further experimental validation.