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.
Background MMRd/Microsatellite instability (MSI) High tumors represent the first tumor-agnostic indication for ICB. Emerging data suggest that the specific MMR protein lost and the mechanism… […]
Characterization of Plasma Cell-Free DNA Variants as ofTumor or Clonal Hematopoiesis Origin in 16,812 Advanced Cancer Patients
