Landscape of EBV-positive gastric cancer

Epstein–Barr virus-positive gastric cancer [EBV (+) GC] is associated with EBV infection and is one of the GC subtypes defined by the Cancer Genome Atlas. EBV (+) GC has several distinct genomic or epigenomic features and clinicopathological characteristics compared with other molecular subtypes of GC. Here, we summarize the unique features of EBV (+) GC including the clinical and histopathological features, and discuss associated genetic and epigenetic aberrations. We also discuss noncoding RNAs [EBV-encoded RNAs and EBV-encoded microRNAs (miRNAs)] derived from EBV-infected cells, which have not been described in detail previously. These noncoding RNAs are defined by their roles; for example, EBV-encoded miRNAs play pivotal roles in oncogenesis and tumor progression in EBV (+) GC. We also discuss recent advances in therapeutic modalities for EBV (+) GC, as well as the potential of EBV infection as a predictive biomarker of the response to anti-PD-1 therapy with immune checkpoint inhibitors. We introduce our recent studies focusing on AT-rich interactive domain 1A gene mutations and programmed death ligand-1 overexpression/ CD274 copy-number amplification, which are recurrently identified in EBV (+) GC. Finally, based on those findings, we propose potential therapeutic options using candidate-targeted therapies against EBV (+) GC.