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Key Findings:
- Comprehensive molecular profiling of 5,175 esophagogastric cancer (EGC) patients identified distinct molecular signatures for early-onset (< 50 years of age, EOEGC, n=530) versus average-onset (AOEGC, n=4,645) tumors.
- EOEGC has increased frequency of CDH1 mutations, ARHGAP26 fusions, enrichment of epithelial mesenchymal transition (EMT) and angiogenesis pathways, decreased MAPK pathway activity, decreased frequency of TMB-high and dMMR/MSI-H, and a unique immune cell infiltrate with decreased M1 macrophages and increased M2 macrophages.
- These unique differential characteristics present therapeutic opportunities but also demonstrate the limitations of currently approved therapies in this subset of patients.
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