Genomic assays for Epstein–Barr virus-positive gastric adenocarcinoma

A small set of gastric adenocarcinomas (9%) harbor Epstein–Barr virus (EBV) DNA within malignant cells, and the virus is not an innocent bystander but rather is intimately linked to pathogenesis and tumor maintenance. Evidence comes from unique genomic features of host DNA, mRNA, microRNA and CpG methylation profiles as revealed by recent comprehensive genomic analysis by The Cancer Genome Atlas Network. Their data show that gastric cancer is not one disease but rather comprises four major classes: EBV-positive, microsatellite instability (MSI), genomically stable and chromosome instability. The EBV-positive class has even more marked CpG methylation than does the MSI class, and viral cancers have a unique pattern of methylation linked to the downregulation of CDKN2A (p16) but not MLH1. EBV-positive cancers often have mutated PIK3CA and ARID1A and an amplified 9p24.1 locus linked to overexpression of JAK2, CD274 (PD-L1) and PDCD1LG2 (PD-L2). Multiple noncoding viral RNAs are highly expressed. Patients who fail standard therapy may qualify for enrollment in clinical trials targeting cancer-related human gene pathways or promoting destruction of infected cells through lytic induction of EBV genes. Genomic tests such as the GastroGenus Gastric Cancer Classifier are available to identify actionable variants in formalin-fixed cancer tissue of affected patients.

• Publication year

  2015

• Venue

  Experimental and Molecular Medicine

• Publication date

  2015-01-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1038/emm.2014.93PMID 25613731PMCID 4314585
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• College of American Pathologists' laboratory standards for next-generation sequencing clinical tests.

  2015cited by this paper
• Epigenetic markers for noninvasive early detection of nasopharyngeal carcinoma by methylation‐sensitive high resolution melting

  2015cited by this paper
• Is gastric lymphoepithelioma-like carcinoma a special subtype of EBV-associated gastric carcinoma? New insight based on clinicopathological features and EBV genome polymorphisms

  2015cited by this paper
• Genetics of gastric cancer

  2014cited by this paper
• PP242 suppresses cell proliferation, metastasis, and angiogenesis of gastric cancer through inhibition of the PI3K/AKT/mTOR pathway

  2014cited by this paper
• Validation and implementation of targeted capture and sequencing for the detection of actionable mutation, copy number variation, and gene rearrangement in clinical cancer specimens.

  2014cited by this paper
• Polymicrobial Infection and Bacterium-Mediated Epigenetic Modification of DNA Tumor Viruses Contribute to Pathogenesis

  2014cited by this paper
• Identification of a DNA Methylome Profile of Esophageal Squamous Cell Carcinoma and Potential Plasma Epigenetic Biomarkers for Early Diagnosis

  2014cited by this paper
• Noninvasive Diagnosis of Actionable Mutations by Deep Sequencing of Circulating Free DNA in Lung Cancer from Never-Smokers: A Proof-of-Concept Study from BioCAST/IFCT-1002

  2014cited by this paper
• Whole-genome sequencing and comprehensive molecular profiling identify new driver mutations in gastric cancer

  2014cited by this paper
• The PI3K/AKT/mTOR pathway is activated in gastric cancer with potential prognostic and predictive significance

  2014cited by this paper
• Multi-platform assessment of transcriptome profiling using RNA-seq in the ABRF next-generation sequencing study

  2014cited by this paper
• DNA methylation subgroups and the CpG island methylator phenotype in gastric cancer: a comprehensive profiling approach

  2014cited by this paper
• Multiplatform analysis of 12 cancer types reveals molecular classification within and across tissues of origin.

  2014cited by this paper
• Comprehensive molecular characterization of gastric adenocarcinoma

  2014cited by this paper
• Combining drugs and biologics to treat nasopharyngeal cancer.

  2014cited by this paper
• Saliva and plasma quantitative polymerase chain reaction-based detection and surveillance of human papillomavirus-related head and neck cancer.

  2014cited by this paper
• Stratification and delineation of gastric cancer signaling by in vitro transcription factor activity profiling and integrative genomics.

  2014cited by this paper
• Regulation of the latent-lytic switch in Epstein-Barr virus.

  2014cited by this paper
• Identification of a new class of small molecules that efficiently reactivate latent Epstein-Barr Virus.

  2014cited by this paper
• Ramucirumab for metastatic gastric or gastroesophageal junction cancer: results and implications of the REGARD trial.

  2014cited by this paper
• Recent advances and future trends in the targeted therapy of metastatic gastric cancer

  2014cited by this paper
• Accumulation of somatic mutations in TP53 in gastric epithelium with Helicobacter pylori infection.

  2014cited by this paper
• Targeted therapies in gastroesophageal cancer.

  2014cited by this paper
• Molecular-targeted therapy for chemotherapy-refractory gastric cancer: a case report and literature review.

  2014cited by this paper
• Microsatellite instability detection by next generation sequencing.

  2014cited by this paper
• RhoA mutations identified in diffuse gastric cancer.

  2014cited by this paper
• Integrated analysis of cancer-related pathways affected by genetic and epigenetic alterations in gastric cancer

  2014cited by this paper
• Integrative identification of Epstein-Barr virus-associated mutations and epigenetic alterations in gastric cancer.

  2014cited by this paper
• Treatment of Nasopharyngeal Carcinoma Cells with the Histone-Deacetylase Inhibitor Abexinostat: Cooperative Effects with Cis-platin and Radiotherapy on Patient-Derived Xenografts

  2014cited by this paper
• Detection of mutations in myeloid malignancies through paired-sample analysis of microdroplet-PCR deep sequencing data.

  2014cited by this paper
• A comprehensive assessment of RNA-seq accuracy, reproducibility and information content by the Sequencing Quality Control consortium

  2014cited by this paper
• Reconstructing and reprogramming the tumor-propagating potential of glioblastoma stem-like cells.

  2014cited by this paper
• Cooperation between Epstein-Barr Virus Immune Evasion Proteins Spreads Protection from CD8+ T Cell Recognition across All Three Phases of the Lytic Cycle

  2014cited by this paper
• An updated review of gastric cancer in the next-generation sequencing era: insights from bench to bedside and vice versa.

  2014cited by this paper
• At the Bench: Helicobacter pylori, dysregulated host responses, DNA damage, and gastric cancer

  2014cited by this paper
• The Role of PI3K/Akt/mTOR Signaling in Gastric Carcinoma

  2014cited by this paper
• Separate quality-control measures are necessary for estimation of RNA and methylated DNA from formalin-fixed, paraffin-embedded specimens by quantitative PCR.

  2014cited by this paper
• A novel selective multikinase inhibitor of ROCK and MRCK effectively blocks cancer cell migration and invasion.

  2014cited by this paper
• DNA methylation in gastric cancer, related to Helicobacter pylori and Epstein-Barr virus.

  2014cited by this paper
• A call to standardize preanalytic data elements for biospecimens.

  2014cited by this paper
• Role of epigenetics in EBV regulation and pathogenesis.

  2014cited by this paper
• Phase II trial of bortezomib alone or in combination with irinotecan in patients with adenocarcinoma of the gastroesophageal junction or stomach

  2014cited by this paper
• Detection of gene rearrangements in targeted clinical next-generation sequencing.

  2014cited by this paper
• Validation of a next-generation sequencing assay for clinical molecular oncology.

  2014cited by this paper
• How prognostic and predictive biomarkers are transforming our understanding and management of advanced gastric cancer.

  2014cited by this paper
• Combining molecular targeted drugs to inhibit both cancer cells and activated stromal cells in gastric cancer.

  2013cited by this paper
• ACMG clinical laboratory standards for next-generation sequencing

  2013cited by this paper
• Differences in Gastric Carcinoma Microenvironment Stratify According to EBV Infection Intensity: Implications for Possible Immune Adjuvant Therapy

  2013cited by this paper
• PD-L1 Expression Is Characteristic of a Subset of Aggressive B-cell Lymphomas and Virus-Associated Malignancies

  2013cited by this paper
• Identification of genes specifically methylated in Epstein–Barr virus‐associated gastric carcinomas

  2013cited by this paper
• Molecular markers for Barrett's esophagus and its progression to cancer

  2013cited by this paper
• Current problems and possible solutions in the treatment of nasopharyngeal carcinoma in Indonesia

  2013cited by this paper
• High-throughput mutation profiling identifies novel molecular dysregulation in high-grade intraepithelial neoplasia and early gastric cancers

  2013cited by this paper
• EBV BILF1 Evolved To Downregulate Cell Surface Display of a Wide Range of HLA Class I Molecules through Their Cytoplasmic Tail

  2013cited by this paper
• The dual PI3K/mTOR inhibitor NVP-BEZ235 enhances nab-paclitaxel antitumor response in experimental gastric cancer

  2013cited by this paper
• mTORC1 inhibition restricts inflammation-associated gastrointestinal tumorigenesis in mice.

  2013cited by this paper
• Preclinical evaluation of the PI3K-mTOR dual inhibitor PF-04691502 as a novel therapeutic drug in nasopharyngeal carcinoma

  2013cited by this paper
• Emerging Roles of Small Epstein-Barr Virus Derived Non-Coding RNAs in Epithelial Malignancy

  2013cited by this paper
• Bortezomib and SAHA Synergistically Induce ROS-Driven Caspase-Dependent Apoptosis of Nasopharyngeal Carcinoma and Block Replication of Epstein–Barr Virus

  2013cited by this paper
• Gastric cancer—molecular and clinical dimensions

  2013cited by this paper
• Towards the goal of personalized medicine in gastric cancer--time to move beyond HER2 inhibition. Part II: Targeting gene mutations and gene amplifications and the angiogenesis pathway.

  2013cited by this paper
• Epstein-Barr virus and host cell methylation: regulation of latency, replication and virus reactivation.

  2013cited by this paper
• Identification of ROS1 rearrangement in gastric adenocarcinoma

  2013cited by this paper
• Towards the goal of personalized medicine in gastric cancer--time to move beyond HER2 inhibition. Part I: Targeting receptor tyrosine kinase gene amplification.

  2013cited by this paper
• Evaluating the effect of unclassified variants identified in MMR genes using phenotypic features, bioinformatics prediction, and RNA assays.

  2013cited by this paper
• Gene methylation in gastric cancer.

  2013cited by this paper
• Spontaneous lytic replication and epitheliotropism define an Epstein-Barr virus strain found in carcinomas.

  2013cited by this paper
• Identification of molecular subtypes of gastric cancer with different responses to PI3-kinase inhibitors and 5-fluorouracil.

  2013cited by this paper
• Expression Profile of MicroRNAs in Epstein-Barr Virus-Infected AGS Gastric Carcinoma Cells

  2013cited by this paper
• CTLA-4 and PD-1/PD-L1 Blockade: New Immunotherapeutic Modalities with Durable Clinical Benefit in Melanoma Patients

  2013cited by this paper
• Genome‐wide identification of Epstein‐Barr virus–driven promoter methylation profiles of human genes in gastric cancer cells

  2013cited by this paper
• Histone deacetylase inhibitors are potent inducers of gene expression in latent EBV and sensitize lymphoma cells to nucleoside antiviral agents.

  2012cited by this paper
• ColoSeq provides comprehensive lynch and polyposis syndrome mutational analysis using massively parallel sequencing.

  2012cited by this paper
• Methylation Subtypes and Large-Scale Epigenetic Alterations in Gastric Cancer

  2012cited by this paper
• Epstein-barr virus infected gastric adenocarcinoma expresses latent and lytic viral transcripts and has a distinct human gene expression profile

  2012cited by this paper
• Relevance, pathogenesis, and testing algorithm for mismatch repair-defective colorectal carcinomas: a report of the association for molecular pathology.

  2012cited by this paper
• Whole-genome reconstruction and mutational signatures in gastric cancer

  2012cited by this paper
• Overexpression of miR-370 and downregulation of its novel target TGFβ-RII contribute to the progression of gastric carcinoma

  2012cited by this paper
• A frequent somatic mutation in CD274 3′‐UTR leads to protein over‐expression in gastric cancer by disrupting miR‐570 binding

  2012cited by this paper
• Quality assurance of RNA expression profiling in clinical laboratories.

  2012cited by this paper
• High-Throughput Mutation Profiling Identifies Frequent Somatic Mutations in Advanced Gastric Adenocarcinoma

  2012cited by this paper
• Methylation profiling of Epstein-Barr virus immediate-early gene promoters, BZLF1 and BRLF1 in tumors of epithelial, NK- and B-cell origins

  2012cited by this paper
• Opportunities and challenges associated with clinical diagnostic genome sequencing: a report of the Association for Molecular Pathology.

  2012cited by this paper
• Assuring the quality of next-generation sequencing in clinical laboratory practice

  2012cited by this paper
• Aberrant expression of miR‐196a in gastric cancers and correlation with recurrence

  2012cited by this paper
• Extended gastritis cystica profunda associated with Epstein‐Barr virus‐positive dysplasia and carcinoma with lymphoid stroma

  2012cited by this paper
• Infection of Epstein–Barr virus in a gastric carcinoma cell line induces anchorage independence and global changes in gene expression

  2012cited by this paper
• The MicroArray Quality Control ( MAQC )-II study of common practices for the development and validation of microarray-based predictive models

  2012cited by this paper
• Diversity of Epstein-Barr virus BamHI-A rightward transcripts and their expression patterns in lytic and latent infections.

  2012cited by this paper
• CD44-SLC1A2 Gene Fusions in Gastric Cancer

  2011cited by this paper
• RCOR2 Is a Subunit of the LSD1 Complex That Regulates ESC Property and Substitutes for SOX2 in Reprogramming Somatic Cells to Pluripotency

  2011cited by this paper
• Epstein-Barr virus genome polymorphisms of Epstein-Barr virus-associated gastric carcinoma in gastric remnant carcinoma in Guangzhou, southern China, an endemic area of nasopharyngeal carcinoma.

  2011cited by this paper
• Global cancer statistics

  2011cited by this paper
• Genomic Loss of miR-486 Regulates Tumor Progression and the OLFM4 Antiapoptotic Factor in Gastric Cancer

  2011cited by this paper
• Clinical outcomes and correlates of TP53 mutations and cancer.

  2010cited by this paper
• Methylation-associated silencing of microRNA-34b/c in gastric cancer and its involvement in an epigenetic field defect.

  2010cited by this paper
• Conserved mutation of Epstein-Barr virus-encoded BamHI-A Rightward Frame-1 (BARF1) gene in Indonesian nasopharyngeal carcinoma

  2010cited by this paper
• The MicroArray Quality Control (MAQC)-II study of common practices for the development and validation of microarray-based predictive models

  2010cited by this paper
• Epstein-Barr virus-specific methylation of human genes in gastric cancer cells

  2010cited by this paper

• Gastric Carcinoma.

  2025cites this paper
• Subtype-Specific Noncoding Ribonucleic Acid Signatures in Gastric Cancer: Insights from The Cancer Genome Atlas-Based Classification

  2025cites this paper
• Efficacy of immunotherapy in ARID1A-mutant solid tumors: a single-center retrospective study

  2024cites this paper
• Research advances in the molecular classification of gastric cancer

  2024cites this paper
• Recognizing the role of Epstein-Barr virus in gastric cancer: transcriptomic insights into malignancy modulation

  2024cites this paper
• Assessing Epstein–Barr virus in gastric cancer: clinicopathological features and prognostic implications

  2023cites this paper
• Role of AT‐rich interaction domain 1A in gastric cancer immunotherapy: Preclinical and clinical perspectives

  2023cites this paper
• FastViFi: Fast and accurate detection of (Hybrid) Viral DNA and RNA

  2022cites this paper
• Human oncogenic viruses: an overview of protein biomarkers in viral cancers and their potential use in clinics

  2022cites this paper
• Gastric cancer with Epstein-Barr virus heterogeneity: Evaluation of the frequency, clinicopathologic features, and genomic profiles.

  2022cites this paper
• Genome-wide DNA methylation profiling of stomach cancer in the ethnic population of Mizoram, North East India.

  2022cites this paper
• An Update on the Pathology and Molecular Features of Hodgkin Lymphoma

  2022cites this paper
• Detection of Epstein Barr Virus DNA in Gastric Adenocarcinoma in Brazzaville

  2022cites this paper
• Epigenetic aberrations by Epstein–Barr virus infection to develop gastric cancer

  2021cites this paper
• EBV‐positive B‐cell lymphomas and lymphoproliferative disorders: Review from the perspective of immune escape and immunodeficiency

  2021cites this paper
• Landscape of EBV-positive gastric cancer

  2021cites this paper
• Viral Manipulation of the Host Epigenome as a Driver of Virus-Induced Oncogenesis

  2021cites this paper
• Epstein-Barr Virus-Associated Gastric Cancer: Old Entity with New Relevance

  2021cites this paper
• EBV miR-BARTs and human lncRNAs: Shifting the balance in competing endogenous RNA networks in EBV-associated gastric cancer.

  2021cites this paper
• Alteration in stemness causes exclusivity between Epstein–Barr virus-positivity and microsatellite instability status in gastric cancer

  2021cites this paper
• Molecular profiling of gastric cancer in a population with high HIV prevalence reveals a shift to MLH1 loss but not the EBV subtype

  2020cites this paper
• EBV-Positive Gastric Cancer: Current Knowledge and Future Perspectives

  2020cites this paper
• Molecular and cellular heterogeneity of gastric cancer explained by methylation-driven key regulators

  2020cites this paper
• ARID1A deficiency in EBV-positive gastric cancer is partially regulated by EBV-encoded miRNAs, but not by DNA promotor hypermethylation.

  2020influential citation
• Epstein-Barr virus-associated gastric cancer: A distinct subtype.

  2020cites this paper
• Decline in circulating viral and human tumor markers after resection of head and neck carcinoma

  2020cites this paper
• Profiling of immune related genes silenced in EBV-positive gastric carcinoma identified novel restriction factors of human gammaherpesviruses

  2020cites this paper
• Molecular Quantification of Epstein-Barr Virus Nuclear Antigen Gene and DNA Methylation Patterns of Human Tumor Suppressor Genes p16 and E-cadherin in Relation to Infection with Helicobacter pylori as Early Prognostic Biomarker for Gastric Tumorgenesis in Patients from Baghdad

  2020cites this paper
• Identification and characterization of an alternative cancer-derived PD-L1 splice variant

  2019cites this paper
• Expression and significance of EBV, ARID1A and PIK3CA in gastric carcinoma

  2019cites this paper
• Genome-wide profiling of Epstein-Barr virus integration by targeted sequencing in Epstein-Barr virus associated malignancies

  2019cites this paper
• PD-L1 expression combined with microsatellite instability/CD8+ tumor infiltrating lymphocytes as a useful prognostic biomarker in gastric cancer

  2019cites this paper
• Association between lncRNA H19 polymorphisms and susceptibility to gastric car- cinoma and EBV-associated gastric carcinoma in Han population in Qingdao

  2019cites this paper
• Risk factors for esophageal cancer: emphasis on infectious agents

  2018cites this paper
• Molecular biomarkers in gastro-esophageal cancer: recent developments, current trends and future directions

  2018cites this paper
• EBV Associated Breast Cancer Whole Methylome Analysis Reveals Viral and Developmental Enriched Pathways

  2018cites this paper
• Immunohistochemical characteristics of bladder cancer in patients with virus-positive tumors

  2018cites this paper
• Prevalent somatic BRCA1 mutations shape clinically relevant genomic patterns of nasopharyngeal carcinoma in Southeast Europe

  2018cites this paper
• Upregulation of programmed death ligand 1 and epidermal growth factor receptor is associated with poor prognosis in gastric cancer

  2018cites this paper
• Role of microRNAs and Exosomes in Helicobacter pylori and Epstein-Barr Virus Associated Gastric Cancers

  2018cites this paper
• Biomarkers for gastric cancer: molecular classification revisited

  2017cites this paper
• Virus de Epstein-Barr y su relación con el desarrollo del cáncer

  2017cites this paper
• Immune Checkpoint Blockade and Gastric Cancer

  2017cites this paper
• CRISPR-Cas9-mediated disruption of PD-1 on human T cells for adoptive cellular therapies of EBV positive gastric cancer

  2017cites this paper
• The Gastric Microbiome and Its Influence on Gastric Carcinogenesis: Current Knowledge and Ongoing Research.

  2017cites this paper
• The Methylation Status and Expression of Epstein-Barr Virus Early Genes BARF1 and BHRF1 in Epstein-Barr Virus-Associated Gastric Carcinomas

  2017influential citation
• The conundrum of the Epstein-Barr virus-associated gastric carcinoma in the Americas

  2017cites this paper
• Epstein-Barr Virus-associated Gastric Cancer and Potential Mechanisms of Oncogenesis.

  2017cites this paper
• The oncogenic role of Epstein–Barr virus‐encoded microRNAs in Epstein–Barr virus‐associated gastric carcinoma

  2017cites this paper
• Lymphoepithelioma-like gastric carcinoma: clinicopathological characteristics and infection status.

  2017cites this paper
• Epstein-Barr Virus–Associated Gastric Carcinoma: The Americas’ Perspective

  2017cites this paper
• HER2 Testing and Clinical Decision Making in Gastroesophageal Adenocarcinoma: Guideline From the College of American Pathologists, American Society for Clinical Pathology, and the American Society of Clinical Oncology.

  2017cites this paper
• Gastric adenocarcinoma microRNA profiles in fixed tissue and in plasma reveal cancer-associated and Epstein-Barr virus-related expression patterns

  2016cites this paper
• HER2 Testing and Clinical Decision Making in Gastroesophageal Adenocarcinoma: Guideline From the College of American Pathologists, American Society for Clinical Pathology, and American Society of Clinical Oncology.

  2016cites this paper
• PD-L1 is an independent prognostic predictor in gastric cancer of Western patients

  2016cites this paper
• A protein and mRNA expression-based classification of gastric cancer

  2016cites this paper
• Report on Carcinogens Monograph on Epstein‑Barr Virus

  2016cites this paper
• Epstein-Barr Virus

  2016cites this paper
• Serological response to Epstein-Barr virus early antigen is associated with gastric cancer and human immunodeficiency virus infection in Zambian adults: a case-control study

  2016cites this paper
• Testing patients with uveal melanoma for herpesvirus infections.

  2016cites this paper
• Epstein-Barr virus BARF1-induced NFκB/miR-146a/SMAD4 alterations in stomach cancer cells

  2016cites this paper
• HER2 Testing and Clinical Decision Making in Gastroesophageal Adenocarcinoma: Guideline From the College of American Pathologists, American Society for Clinical Pathology, and American Society of Clinical Oncology.

  2016cites this paper
• HER 2 Testing and Clinical Decision Making in Gastroesophageal Adenocarcinoma Guideline

  2016cites this paper
• KRAS, BRAF and gastric cancer

  2015cites this paper
• Are Epstein-Barr Virus-positive and -negative Gastric Carcinomas, With Lymphoid Stroma, Single Entity or Different Entities?

  2015cites this paper
• Noncoding Genomics in Gastric Cancer and the Gastric Precancerous Cascade: Pathogenesis and Biomarkers

  2015influential citation
• Methylome analysis reveals dysregulated developmental and viral pathways in breast cancer

  2015cites this paper
• PD-1 and PD-L1 blockade in gastrointestinal malignancies.

  2015cites this paper
• Distinct Viral and Mutational Spectrum of Endemic Burkitt Lymphoma

  2015cites this paper
• Targeted therapy for advanced gastric cancer: A review of current status and future prospects.

  2015cites this paper
• Epstein–Barr Virus

  2014cites this paper