title: Update on Epstein-Barr virus and gastric cancer (review).
abstract: Epstein-Barr virus-associated gastric carcinoma (EBVaGC) is a distinct subtype that accounts for nearly 10% of gastric carcinomas. EBVaGC is defined by monoclonal proliferation of carcinoma cells with latent EBV infection, as demonstrated by EBV-encoded small RNA (EBER) in situ hybridization. EBVaGC has characteristic clinicopathological features, including predominance among males, a proximal location in the stomach, lymphoepithelioma-like histology and a favorable prognosis. EBVaGC belongs to latency type I or II, in which EBERs, EBNA-1, BARTs, LMP-2A and BART miRNAs are expressed. Previous studies have shown that some EBV latent genes have oncogenic properties. Recent advances in genome-wide and comprehensive molecular analyses have demonstrated that both genetic and epigenetic changes contribute to EBVaGC carcinogenesis. Genetic changes that are characteristic of EBVaGC include frequent mutations in PIK3CA and ARID1A and amplification of JAK2 and PD-L1/L2. Global CpG island hypermethylation, which induces epigenetic silencing of tumor suppressor genes, is also a unique feature of EBVaGC and is considered to be crucial for its carcinogenesis. Furthermore, post-transcriptional gene expression regulation by cellular and/or EBV-derived microRNAs has attracted considerable attention. These abnormalities result in significant alterations in gene expression related to cell proliferation, apoptosis, migration and immune signaling pathways. In the present review we highlight the latest findings on EBVaGC from clinicopathological and molecular perspectives to provide a better understanding of EBV involvement in gastric carcinogenesis.
authors: Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
authors: Aya
authors: A
authors: Shinozaki-Ushiku
authors: Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
authors: Akiko
authors: A
authors: Kunita
authors: Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
authors: Masashi
authors: M
authors: Fukayama
mesh_terms: D019175:DNA Methylation; D044127:Epigenesis, Genetic; D020031:Epstein-Barr Virus Infections / Q000235:genetics / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D004854:Herpesvirus 4, Human / Q000502:physiology*; D006801:Humans; D008297:Male; D012737:Sex Factors; D013274:Stomach Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology / Q000821:virology*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D025521:Tumor Suppressor Proteins