Molecular features and translational outlook for Epstein-Barr virus-associated gastric cancer

Epstein-Barr Virus (EBV) was the first discovered human tumor virus and is the etiological agent of B cell lymphomas and also epithelial cancers. Indeed, nearly 10% of gastric cancers worldwide are EBV-positive and display unique molecular, epigenetic, and clinicopathological features. EBV-positive gastric cancers display the highest rate of host genome methylation of all tumor types studied and harbor recurrent mutations activating PI3Kα, silencing ARID1A, and amplifying PD-L1. While EBV infection of B cells can be studied efficiently, de novo epithelial cell infection is much more difficult. We propose that new culture models including 3D-based gastric organoids and xenografts can bring new insight into EBV-induced gastric carcinogenesis and will lead to improved precision medicine-based therapies for patients with EBV-positive gastric cancer.