ObjectivesUsing a comprehensive dataset derived from the American Association for Cancer Research (AACR) Project Genomics, Evidence, Neoplasia, Information, and Exchange (GENIE), we sought to demonstrate the genetic characteristics of esophageal squamous cell cancer (ESCC) and esophageal adenocarcinoma (EAC). MethodologyData were extracted from cBioPortal for cancer genomics (genie.cbioportal.org). Patients with EAC and squamous cell carcinoma were selected. To compare categorical variables, either the chi-square or KruskalWallis test was used. The Benjamini-Hochberg method was applied to correct P-values, and consequently, false discovery rate-adjusted q-values were computed. When the q-value was <0.05, the P-value < 0.05 was accepted as statistically significant.ResultsIn this study, 1,381 patients with EAC and 312 patients with ESCC were analyzed. Gene alterations were different between the two groups. In EAC, genetic alterations were detected in ERBB2, KRAS, SMAD4, and TACC3 genes, whereas ESCC exhibited alterations in CCDN1, NFE2L2, FGF19, FGF3, FGF4, NOTCH1, and CDKN2B genes.ConclusionsNotably, this study showed distinct differences in gene alterations between ESCC and EAC, thereby enhancing our understanding of the genetic landscape of these tumors. Further research is required to elucidate the functional implications of these genetic variations to develop targeted therapies that can improve the prognosis of patients with esophageal cancer.