The study provides a comprehensive molecular characterization of 295 primary gastric adenocarcinomas as part of the Cancer Genome Atlas (TCGA) project. The analysis identifies four major genomic subtypes of gastric cancer: EBV-infected tumors, microsatellite instability (MSI) tumors, genomically stable tumors, and chromosomally unstable tumors. Each subtype is characterized by distinct molecular features, including genetic mutations, DNA methylation patterns, and chromosomal alterations. For example, EBV-positive tumors show recurrent PIK3CA mutations, extreme DNA hypermethylation, and amplification of JAK2, CD274 (PD-L1), and PDCD1LG2 (PD-L2). MSI tumors exhibit elevated mutation rates and hypermethylation, while genomically stable tumors are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins. Chromosomally unstable tumors show marked aneuploidy and focal amplification of receptor tyrosine kinases. These findings provide a roadmap for patient stratification and targeted therapy trials.The study provides a comprehensive molecular characterization of 295 primary gastric adenocarcinomas as part of the Cancer Genome Atlas (TCGA) project. The analysis identifies four major genomic subtypes of gastric cancer: EBV-infected tumors, microsatellite instability (MSI) tumors, genomically stable tumors, and chromosomally unstable tumors. Each subtype is characterized by distinct molecular features, including genetic mutations, DNA methylation patterns, and chromosomal alterations. For example, EBV-positive tumors show recurrent PIK3CA mutations, extreme DNA hypermethylation, and amplification of JAK2, CD274 (PD-L1), and PDCD1LG2 (PD-L2). MSI tumors exhibit elevated mutation rates and hypermethylation, while genomically stable tumors are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins. Chromosomally unstable tumors show marked aneuploidy and focal amplification of receptor tyrosine kinases. These findings provide a roadmap for patient stratification and targeted therapy trials.