ArticleGenome medicine2021
The genomic architecture of EBV and infected gastric tissue from precursor lesions to carcinoma.
Article in Genome medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 35 citations in OpenAlex.
- Review
- EBV hijacks the metabolic function of CD73 to resist the antitumor function of NK cells.NPJ precision oncology · 2026Article
- Comprehensive analysis of the gastric metatranscriptome reveals specific viral signatures associated with gastric cancer.International microbiology : the official journal of the Spanish Society for Microbiology · 2026Article
- Intra-tumoral microbiota: Key modulators of tumor immunity and therapeutic potential.Genes & diseases · 2026Review
- The mycobiome, virome and archaeome in gastrointestinal cancers: molecular pathogenesis and therapeutic intervention.Molecular cancer · 2026Review
- EBV-miR-BART14-3p Targets LACTB to Enhance Gastric Cancer Cell Proliferation and Migration.Biochemical genetics · 2026Article
- Integrated Bulk and Single-Cell Transcriptomic Analyses Identify a Five-Gene Signature Associated With Prognosis and the Tumor Microenvironment in Epstein-Barr Virus-Associated Gastric Cancer.Genetics research · 2026Article
- The Double-Edged Sword of Genomic DNA Methylation: Orchestrating Gastric Carcinogenesis and Shaping Precision Oncology.Oncology research · 2026Review
- Article
- Incidence, Prognostic Factors, and Treatment Impact on Survival in Natural Killer/T-Cell Lymphoma: Population-Based Study in the United States.JMIR formative research · 2025Article
- Demographic/clinicopathological characteristics and prognosis of resectable Epstein-Barr virus-associated gastric cancer: a nested case-control study from an Eastern China.Frontiers in oncology · 2025Article
- The role of MAPK pathway in gastric cancer: unveiling molecular crosstalk and therapeutic prospects.Journal of translational medicine · 2024Review
- Advancement in Multi-omics approaches for Uterine Sarcoma.Biomarker research · 2024Review
- Hyperactivation of mTOR/eIF4E Signaling Pathway Promotes the Production of Tryptophan-To-Phenylalanine Substitutants in EBV-Positive Gastric Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Gamma-glutamyl transferase secreted by Helicobacter pylori promotes the development of gastric cancer by affecting the energy metabolism and histone methylation status of gastric epithelial cells.Cell communication and signaling : CCS · 2024Article
- Epstein-Barr virus causes vascular abnormalities in epithelial malignancies through upregulating ANXA3-HIF-1α-VEGF pathway.Oncogene · 2024Article
- Hierarchical learning of gastric cancer molecular subtypes by integrating multi-modal DNA-level omics data and clinical stratification.Quantitative biology (Beijing, China) · 2024Article
- EBV DNA methylation profiles and its application in distinguishing nasopharyngeal carcinoma and nasal NK/T-cell lymphoma.Clinical epigenetics · 2024Article
- The viral etiology of EBV-associated gastric cancers contributes to their unique pathology, clinical outcomes, treatment responses and immune landscape.Frontiers in immunology · 2024Review
- Deciphering gastric inflammation-induced tumorigenesis through multi-omics data and AI methods.Cancer biology & medicine · 2023Review
Corrections and comments
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Authors and funding
24 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEpstein-Barr virus (EBV)-associated gastric carcinomas (EBVaGCs) present unique molecular signatures, but the tumorigenesis of EBVaGCs and the role EBV plays during this process remain poorly understood.
methodsWe applied whole-exome sequencing, EBV genome sequencing, and whole-genome bisulfite sequencing to multiple samples (n = 123) derived from the same patients (n = 25), which covered saliva samples and different histological stages from morphologically normal epithelial tissues to dysplasia and EBVaGCs. We compared the genomic landscape between EBVaGCs and their precursor lesions and traced the clonal evolution for each patient. We also analyzed genome sequences of EBV from samples of different histological types. Finally, the key molecular events promoting the tumor evolution were demonstrated by MTT, IC50, and colony formation assay in vitro experiments and in vivo xenograft experiments.
resultsOur analysis revealed increasing mutational burden and EBV load from normal tissues and low-grade dysplasia (LD) to high-grade dysplasia (HD) and EBVaGCs, and oncogenic amplifications occurred late in EBVaGCs. Interestingly, within each patient, EBVaGCs and HDs were monoclonal and harbored single-strain-originated EBV, but saliva or normal tissues/LDs had different EBV strains from that in EBVaGCs. Compared with precursor lesions, tumor cells showed incremental methylation in promotor regions, whereas EBV presented consistent hypermethylation. Dominant alterations targeting the PI3K-Akt and Wnt pathways were found in EBV-infected cells. The combinational inhibition of these two pathways in EBV-positive tumor cells confirmed their synergistic function.
conclusionsWe portrayed the (epi) genomic evolution process of EBVaGCs, revealed the extensive genomic diversity of EBV between tumors and normal tissue sites, and demonstrated the synergistic activation of the PI3K and Wnt pathways in EBVaGCs, offering a new potential treatment strategy for this disease.
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