title: Mobile elements and viral integrations prompt considerations for bacterial DNA integration as a novel carcinogen.
abstract: Insertional mutagenesis has been repeatedly demonstrated in cancer genomes and has a role in oncogenesis. Mobile genetic elements can induce cancer development by random insertion into cancer related genes or by inducing translocations. L1s are typically implicated in cancers of an epithelial cell origin, while Alu elements have been implicated in leukemia as well as epithelial cell cancers. Likewise, viral infections have a significant role in cancer development predominantly through integration into the human genome and mutating or deregulating cancer related genes. Human papilloma virus is the best-known example of viral integrations contributing to carcinogenesis. However, hepatitis B virus, Epstein-Barr virus, and Merkel cell polyomavirus also integrate into the human genome and disrupt cancer related genes. Thus far, the role of microbes in cancer has primarily been attributed to mutations induced through chronic inflammation or toxins, as is the case with Helicobacter pylori and enterotoxigenic Bacteroides fragilis. We hypothesize that like mobile elements and viral DNA, bacterial and parasitic DNA may also integrate into the human somatic genome and be oncogenic. Until recently it was believed that bacterial DNA could not integrate into the human genome, but new evidence demonstrates that bacterial insertional mutagenesis may occur in cancer cells. Although this work does not show causation between bacterial insertions and cancer, it prompts more research in this area. Promising new sequencing technologies may reduce the risk of artifactual chimeric sequences, thus diminishing some of the challenges of identifying novel insertions in the somatic human genome.
authors: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA.
authors: Kelly M
authors: KM
authors: Robinson
authors: Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, USA; Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA; Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA. Electronic address: jdhotopp@som.umaryland.edu.
authors: Julie C
authors: JC
authors: Dunning Hotopp
mesh_terms: D000818:Animals; D001424:Bacterial Infections / Q000235:genetics* / Q000382:microbiology; D002472:Cell Transformation, Viral; D004269:DNA, Bacterial / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D006801:Humans; D020071:Interspersed Repetitive Sequences; D016254:Mutagenesis, Insertional; D009369:Neoplasms / Q000235:genetics* / Q000382:microbiology / Q000473:pathology / Q000821:virology; D010641:Phenotype; D012307:Risk Factors; D014412:Tumor Virus Infections / Q000235:genetics* / Q000821:virology; D016662:Virus Integration
chemical_list: D004269:DNA, Bacterial
keywords: Bacteria; Lateral gene transfer; Mobile elements; Parasites; Viruses