Distinct differences in genomic profile of gastric and gastroesophageal junction adenocarcinoma.

Abstract

345 Background: Gastroesophageal junction cancer (GEJC) and gastric cancer (GC) are frequently studied together as one disease. Genomic profiles between the two disease sites have not been well characterized. We aimed to characterize molecular differences between the two disease sites. Methods: We collected data between January 2010 and December 2019 from a prospectively maintained database of GEJC and GC at our center. GEJC was defined according to the Siewert type 1 to 3 classification. Patients who underwent surgical resection and had MSK-IMPACT (MSK-Integrated Mutation Profiling of Actionable Cancer Targets) sequencing performed on their primary tumor were included in this analysis. Results: Two hundred and seventy-four samples were analyzed; 156 (56.9%) GEJC and 118 (43.1%) GC patients. Regarding molecular subtypes, the GEJC group had a higher frequency of chromosomally instable tumors compared to the GC cohort (55.1% vs. 25.4%, p < 0.001). The fraction of genome altered (FGA) was significantly higher in the GEJC group (p < 0.001). TP53 (75.3% vs. 31.9%, p < 0.001, q < 0.001), CDKN2A (17.1% vs. 4.3%, p = 0.002, q = 0.02), and MDM2 (6.8% vs. 0%, p = 0.007, q = 0.033) were more frequently altered in the GEJC group, whereas CDH1 (2.7% vs. 9.6%, p = 0.037, q = 0.118) and RHOA (0% vs. 6.4%, p = 0.003, q = 0.02) were more frequently altered in the GC group. The GEJC group also had a higher frequency of alterations in the cell cycle pathway compared to the GC patients (36.3% vs. 11.7%, p < 0.001, q < 0.001). Conclusions: There are distinct differences in genomic profiles between GEJC and GC with a higher frequency of mutations in TP53, CDKN2A, MDM2, and cell cycle pathway in the GEJC patients, that may have potential implications in evaluating optimal treatment strategies with targeted therapy.