Rate of gene fusion/rearrangement identification in GI cancers as sequencing evolved from limited panels to whole exome sequencing.

809 Background: Gene fusion/rearrangements occur at a frequency of 0-15% in GI system cancers. Detection and treatment of fusion genes such as NTRK, FGFR2, NRG1 and RET fusions are included in NCCN guidelines and are commonly detected using next generation sequencing (NGS). NGS panels have continued to expand over time, which should result in increases in the identification of gene fusions. The aims of this study were to describe the percent of patients with advanced GI tumors undergoing NGS with identified gene rearrangements across time as panels expanded. Methods: The study included 7237 patients in the Kaiser Permanente Northern California Integrated Health System receiving care for advanced GI cancers from 2017 to Aug 2024, whose tumors samples were evaluated using NGS (Stomach=926, Colorectal=2792, Gallbladder=569, Esophagus=761, liver=218, Pancreas=1971). Results: A total of 231 patients (3.2%) were identified with a gene rearrangement, including 4.6% in stomach(N=43), 2.8% in colorectal(N=78), 8.9% in gallbladder(N=24), 5.3% in esophagus(N=40), and 1.9% in pancreatic (N=38 ). Rearrangements included NTRK1/2/3, FGFR2/3, NRG, ALK, ROS, CLDN18-ARHGAP, RSPO2/3, DNAJB1-PRKACA, BRAF, MET and RET. The numbers per year were (see table). Conclusions: The use of more comprehensive NGS panels such as WES did not appear to increase the detection rate for fusion/rearrangements. In resource limited settings, limited panels may suffice. The number of GI cancer patients getting NGS testing has increased over time. Gene rearrangements/fusions identified per year. YEAR 2018 2019 2020 2021 2022 2023 2024 (Jan – Aug) Gene Rearrangement identified 29 37 43 55 54 62 38 TOTAL GI Cancer Samples Sequenced 610 858 900 1047 1249 1181 785 Percentage 4.75% 4.31% 4.78% 5.25% 4.32% 5.25% 4.84%