Detection of targetable fusion alterations in gastric cancer in the Chinese population.

Abstract

e16061 Background: Despite a decreasing incidence and mortality globally, gastric cancer (GC) remains a main threat to public health, especially in China. Consistently, drug therapy is a big challenge for gastric cancer. Although HER2-directed therapy and immune checkpoint inhibitors have achieved great success, other valid targeted drugs are required to develop. Targeted drugs of NTRK gene fusion have been approved in solid tumors including GC by FDA. Moreover, FDA has granted Zenocutuzumab fast-track approval for patients with NRG1 gene fusion in solid tumors. However, in China, gene fusion and functional characterization have not been reported to date in detail. Methods: In order to estimate the fraction of patients who may benefit from targeted drugs, we retrospectively analyzed the fusion alterations in gastric cancer tissue samples from 955 Chinese patients. Remarkably, as fusion partners, all genes included fusion analysis possess experimental or approved drugs. The clinicopathological characteristics were retrieved from the medical records in hospital. Chi-square analysis was used to investigate the relationship of gene fusions with drivers mutations, MSI, TMB and MMR. Results: We found 2.82% (27/955) of patients harboring fusion genes, including MET, ROS1, ALK, FGFR1/2, NTRK, BRAF, EGFR and so on. Among them, EML4-ALK, EWSR1-FLI1 and EGFR-SEPTIN14 have been described in other studies, but 88.9% (24/27) fusion genes are previously unreported. Sequencing results indicate that fusion genes are significantly enriched in patients with ERBB2 gene amplification. In addition, there is no obvious correlation between the positive rate of gene fusion and clinical features including age and gender. Similarly, MSI status, TMB and MMR are included for correlation analysis with gene fusion. Unfortunately, the results are not statistically significant. Conclusions: Our work characterizes the landscape of targetable fusion alterations in gastric cancer in the Chinese population and investigates that targetable fusion testing should be advised to patients with disease progression after receiving standard therapy.