权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Extent and Significance of Bacterial DNA Integrations in the Human Cancer Genome

人类癌症基因组中细菌 DNA 整合的程度和意义

基本信息

批准号：
9147561
负责人：
Julie Dunning Hotopp
金额：
$ 73.43万
依托单位：
UNIVERSITY OF MARYLAND BALTIMORE
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-09-22 至 2020-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9147561
关键词：
Acinetobacter Acute Myelocytic Leukemia Address Aphids Bacteria Bacterial DNA Bioinformatics CEACAM5 gene CRISPR/Cas technology Cell Line Cells Chimera organism Clonal Expansion Colon Communities DNA DNA Integration Data Data Set Detection Disease Event Exposure to Frequencies Gastric Adenocarcinoma Gene Expression Genes Genetic Transcription Genome Genomic DNA Genomics Health Human Human Chromosomes Human Genome Human Papillomavirus In Vitro Infection Infectious Agent Insertional Mutagenesis Invertebrates Knowledge Lead Link Luciferases Malignant Neoplasms Malignant neoplasm of cervix uteri Measures Metadata Mitochondria Mitochondrial DNA Modeling Nucleic Acids Oncogenic Paper Patients Phenotype Prevalence Proto-Oncogenes Pseudomonas Reporter Research Resources Role Running Sampling Scientist Seminal Somatic Mutation Specimen Stomach System Techniques Testing The Cancer Genome Atlas Therapeutic Uses Tissues Transcript Untranslated Regions Up-Regulation Vaccines Validation Vertebrates Wolbachia Work base cancer genome cohort endosymbiont fighting genome sequencing human genome sequencing improved innovation invertebrate genome invertebrate host malignant stomach neoplasm microbiome prevent promoter reference genome research study stem tool transcriptome sequencing tumor tumorigenesis viral DNA virtual

项目摘要

DESCRIPTION (provided by applicant): The integration of exogenous DNA into the human genome can cause somatic mutations associated with oncogenesis. For example, the insertion of HPV DNA into human chromosomes is the single most important event leading to tumorigenesis in cervical cancer. It is also now preventable with vaccines against HPV. In contrast to viral DNA integrations, the instances and repercussions of bacterial DNA integration into the somatic human genome are less clear. Yet bacterial DNA integrations found to be associated with tumorigenesis could also be prevented using therapeutics like vaccines that limit exposure to the bacteria. This proposal has three objectives aimed at addressing our gap in knowledge about bacterial DNA integrations. First, virtual machines will be developed for LGTSeek and LGTview, our bioinformatics tools that we have used previously to detect bacterial DNA integrations in human genome sequencing projects. These virtual machines would enable these tools to be run by a wide variety of users, from the bioinformatically savvy to the naïve. This provides a resource to the community to enable detection of such integrations by a wider variety of scientists. In addition, LGTSeek and LGTView will be used to further interrogate publicly available cancer genome data where such integrations are likely to occur because the tissues are exposed to the microbiome (e.g. colon). Second, genome and transcriptome sequencing will be undertaken of new stomach adenocarcinoma samples and acute myeloid leukemia samples. This objective is aimed at reproducing previous results that suggest the presence of bacterial DNA integrations. These sequencing efforts would include control samples with exogenous bacterial nucleic acids added to the sample in order to quantify the formation of chimeras in modern sequencing techniques. Third, the effect that previously detected bacterial DNA integrations have on transcription will be interrogated using luciferase reporter constructs. Integrations that lead to up-regulation of the gene will be further interrogated by reconstructing the integrations in cells using the CRISPR/Cas9 system. Collectively, this research is expected to improve our understanding of the extent and significance of bacterial DNA integrations in the somatic human genome.