Abstract 1959P
Background
Inhibitors of several targetable gene rearrangements have demonstrated promising results in solid tumors. However, the distribution of targetable rearrangements has not been well understood in Chinese gastrointestinal cancer patients.
Methods
Tumor specimen and/or cell-free DNA samples were collected from 7152 patients with gastrointestinal cancer for Next-generation sequencing. Single-nucleotide variants, insertions/deletions, copy number variations and gene rearrangements of selected genes were assessed. Microsatellite status were evaluated in 5717/7152 patients. Potentially targetable rearrangements (PTRs) were identified according to OncoKB database.
Results
Totally, 144/7152 (2%) patients harbored one or more rearrangements of the eleven genes including ALK, BRAF, EGFR, FGFR2/3, MET, NTRK1-3, RET and ROS1. PTRs were identified in 85/144 (59%) of patients and occurred in a rate of 1.21% in colorectal cancer, 1.46% in gastric cancer, 0.78% in gastrointestinal stromal tumor (GIST), and 0.39% in small bowel cancer. No PTR was detected in gastroesophageal junction cancer and neuroendocrine. Among the PTRs, FGFR2 was the most frequent rearranged gene, followed by BRAF (20.9%), NTRK1 (19.8%), ALK (12.8%), RET (12.8%), EGFR (7.0%), FGFR3 (3.5%), MET (2.3%), ROS1 (2.3%) and NTRK3 (1.2%). In colorectal cancer, PTRs of BRAF (15, 0.31%), NTRK1 (12, 0.25%) and RET (10, 0.21%) were the most frequent. In gastric cancer, PTRs of FGFR2 (13, 0.79%) was the most common rearrangement. In addition, double PTRs were detected in nine patients, including TIMM23B-RET and NCOA4-RET in colorectal cancer (N=5); EML4-ALK and ALK-intergenic region in colorectal cancer, TPM4-ALK and FGFR3-TACC3 in colorectal cancer, GPHN-ALK and ALK-PPP1CB in small bowel cancer, PPFIBP1-ALK and ALK-EDAR in GIST (N=5 each). Compared with patients with microsatellite stable, PTRs tended to occur in gastrointestinal cancer patients with microsatellite instability (8.43% vs 0.63%, P<0.0001).
Conclusions
The study revealed the distribution of PTRs in Chinese gastrointestinal cancer patients and 1.19% patients may benefit from matched PTR-inhibitors. Further study is required to validate the correlation of the presence of gene PTRs and microsatellite instability.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.