Gastric cancer is a leading cause of cancer deaths, but analysis of its molecular and clinical characteristics has been complicated by histological and aetiological heterogeneity. Here we describe a comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project. We propose a molecular classification dividing gastric cancer into four subtypes: tumours positive for Epstein–Barr virus, which display recurrent PIK3CA mutations, extreme DNA hypermethylation, and amplification of JAK2, CD274 (also known as PD-L1) and PDCD1LG2 (also knownasPD-L2); microsatellite unstable tumours, which show elevated mutation rates, including mutations of genes encoding targetable oncogenic signalling proteins; genomically stable tumours, which are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins; and tumours with chromosomal instability, which show marked aneuploidy and focal amplification of receptor tyrosine kinases. Identification of these subtypes provides a roadmap for patient stratification and trials of targeted therapies.

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Background Endoscopic screening for esophageal neoplasia can identify patients eligible for early intervention for pre-cancerous lesions. Unsedated transnasal esophagoscopy may provide an efficient and accurate endoscopic assessment with fewer risks and less cost compared to conventional upper endoscopy. Objective To assess the feasibility, safety, acceptability and yield of unsedated transnasal esophagoscopy in a primary care population. Design Multi-center, prospective, cross-sectional study. Setting Two outpatient tertiary centers. Patients General medical clinic population between the ages of 40 and 85. Interventions Unsedated, office-based transnasal esophagoscopy. Main outcomes measurements 1) Procedure yield, 2) Completeness of examination, 3) Procedure length, 4) Adverse events and complications, 5) Choking, gagging, pain or anxiety during the examination, and 6) Overall tolerability Results Four hundred and twenty-six participants (mean age 55.8 ± 9.5, 43% male) enrolled in the study, and 422 (99%) completed the examination. Mean examination time was 3.7 ± 1.8 minutes. There were no serious adverse events and 12 participants (2.8%) reported minor complications. Participants reported minimal choking, gagging, pain or anxiety. The examination was well tolerated by most participants. Overall, 38% of subjects had an esophageal finding that changed management (34% erosive esophagitis, 4% Barrett’s esophagus). Limitations Nonrandomized study; tertiary centers only; self-selected population with a large proportion reporting esophageal symptoms. Conclusions Unsedated transnasal esophagoscopy is a feasible, safe, and well-tolerated method to screen for esophageal disease in a primary care population. Endoscopic findings are common in this patient population.

The use of genomic predictors of response to cisplatin and pemetrexed can be incorporated into strategies to optimize therapy for advanced solid tumors.