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Successful identification and targeting of oncogenic gene fusion is a major breakthrough in cancer treatment. Here, we investigate the therapeutic implications and feasibility of using a targeted RNA sequencing panel to identify fusion genes in gastrointestinal and rare cancers. From February through December 2017, patients with gastrointestinal, hepatobiliary, gynecologic, sarcoma, or rare cancers were recruited for a clinical sequencing project at Samsung Medical Center (NCT #02593578). The median age of the patients was 58 years (range, 31–81 years), and the male-to-female ratio was 1.3 : 1. A total of 118 patients passed the quality control process for a next-generation sequencing- (NGS-) based targeted sequencing assay. The NGS-based targeted sequencing assay was performed to detect gene fusions in 36–53 cancer-implicated genes. The following cancer types were included in this study: 28 colorectal cancers, 27 biliary tract cancers, 25 gastric cancers, 18 soft tissue sarcomas, 9 pancreatic cancers, 6 ovarian cancers, and 9 other rare cancers. Strong fusion was detected in 25 samples (21.2%). We found that 5.9% (7/118) of patients had known targetable fusion genes involving  NTRK1  ( n =3),  FGFR  ( n =3), and  RET  ( n =1), and 10.2% (12/118) of patients had potentially targetable fusion genes involving  RAF1  ( n =4),  BRAF  ( n =2),  ALK  ( n =2),  ROS1  ( n =1),  EGFR  ( n =1), and  CLDN18  ( n =2). Thus, we successfully identified a substantial proportion of patients harboring fusion genes by RNA panel sequencing of gastrointestinal/rare cancers. Targetable and potentially targetable involved fusion genes were  NTRK1 ,  RET ,  FGFR3 ,  FGFR2 ,  BRAF ,  RAF1 ,  ALK ,  ROS1 , and  CLDN18 . Detection of fusion genes by RNA panel sequencing may be beneficial in refractory patients with gastrointestinal/rare cancers.

Detection of Fusion Genes Using a Targeted RNA Sequencing Panel in Gastrointestinal and Rare Cancers