Molecular Characterization Of Early Vs. Late Onset Gastroesophageal Cancers.

46Background: Gastric and esophageal adenocarcinomas (GA and EA) in young patients (pts) are more likely driven by genetic factors than environmental carcinogens. Tumor molecular variations defining individual differences in age of onset have not been well elucidated. Methods: Protein expression (IHC), gene amplification (ISH), and next generation sequencing (NGS) were tested on GA and EA tumors. Tumor mutational load (TML) was calculated using only somatic nonsynonymous missense mutations sequenced with a 592-gene panel. Chi-square and t-tests were used for comparative analyses. Results: In total, 1670 tumors were examined; older (age u003e60) vs. younger (u003c45)comparisons were made in 599 GA and 491 EA (Table). In GA, significantly higher TOPO2A and TOPO1 expression was seen in older vs. younger pts, while higher mutation rates of FGFR2, IDH1, and NRAS were seen in younger pts. In EA, EGFR expression was higher in the older pts, while ATM and BRCA1 mutations were higher in the younger pts. When only primary ...