title: Epstein-Barr virus-positive gastric cancer: a distinct molecular subtype of the disease?
abstract: Approximately 90% of the world population is infected by Epstein-Barr virus (EBV). Usually, it infects B lymphocytes, predisposing them to malignant transformation. Infection of epithelial cells occurs rarely, and it is estimated that about to 10% of gastric cancer patients harbor EBV in their malignant cells. Given that gastric cancer is the third leading cause of cancer-related mortality worldwide, with a global annual incidence of over 950,000 cases, EBV-positive gastric cancer is the largest group of EBV-associated malignancies. Based on gene expression profile studies, gastric cancer was recently categorized into four subtypes; EBV-positive, microsatellite unstable, genomically stable and chromosomal instability. Together with previous studies, this report provided a more detailed molecular characterization of gastric cancer, demonstrating that EBV-positive gastric cancer is a distinct molecular subtype of the disease, with unique genetic and epigenetic abnormalities, reflected in a specific phenotype. The recognition of characteristic molecular alterations in gastric cancer allows the identification of molecular pathways involved in cell proliferation and survival, with the potential to identify therapeutic targets. These findings highlight the enormous heterogeneity of gastric cancer, and the complex interplay between genetic and epigenetic alterations in the disease, and provide a roadmap to implementation of genome-guided personalized therapy in gastric cancer. The present review discusses the initial studies describing EBV-positive gastric cancer as a distinct clinical entity, presents recently described genetic and epigenetic alterations, and considers potential therapeutic insights derived from the recognition of this new molecular subtype of gastric adenocarcinoma.
authors.affiliation: Departamento de Oncologia Clínica, Hospital Mater Dei, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Alexandre Andrade Dos Anjos
authors.initials: AA
authors.lastname: Jácome
authors.affiliation: Departamento de Oncologia Clínica, Hospital Mater Dei, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Enaldo Melo de
authors.initials: EM
authors.lastname: Lima
authors.affiliation: Departamento de Oncologia Clínica, Hospital Mater Dei, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Ana Izabela
authors.initials: AI
authors.lastname: Kazzi
authors.affiliation: Departamento de Oncologia Clínica, Hospital Mater Dei, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Gabriela Freitas
authors.initials: GF
authors.lastname: Chaves
authors.affiliation: Departamento de Oncologia Clínica, Hospital Mater Dei, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Diego Cavalheiro de
authors.initials: DC
authors.lastname: Mendonça
authors.affiliation: Departamento de Oncologia Clínica, Hospital Mater Dei, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Marina Mara
authors.initials: MM
authors.lastname: Maciel
authors.affiliation: Faculdade de Medicina de Ribeirão Preto, Departamento de Cirurgia e Anatomia, Universidade de São Paulo, Ribeirão Preto, São Paulo, Brazil.
authors.forename: José Sebastião Dos
authors.initials: JS
authors.lastname: Santos
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000821:virology*; D044127:Epigenesis, Genetic; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D013274:Stomach Neoplasms / Q000235:genetics / Q000821:virology*