Tropomyosin-Related Kinase Fusions in Gastrointestinal Stromal Tumors (vol 14, 2659, 2022)

Simple Summary The canonical mutations in gastrointestinal stromal tumors (GISTs) are typically activating mutations in KIT and platelet-derived growth factor receptor alpha (PDGFRA). Imatinib, the treatment of choice for GISTs, shows a lower response in KIT/PDGFRA wild-type GISTs. Neurotrophic tyrosine receptor kinase (NTRK) fusion, which can be treated with an NTRK target agent, has been reported in KIT/PDGFRA wild-type GISTs, and, therefore, the Yonsei Cancer Center analyzed NTRK fusion incidence in KIT/PDGFRA wild-type GISTs. At the Yonsei Cancer Center, NTRK fusion was confirmed in 16% of cases. Confirmation of NTRK fusion in KIT/PDGFRA wild-type GISTs provides important information for improving therapeutic outcomes. NTRK fusion was confirmed in 16% of KIT/PDGFRA wild-type GIST cases at the Yonsei Cancer Center. Confirmation of NTRK fusion in KIT/PDGFRA wild-type GISTs will improve therapeutic outcomes. The canonical mutations in gastrointestinal stromal tumors (GISTs) are typically activating mutations in KIT and platelet-derived growth factor receptor alpha (PDGFRA). GISTs with non-canonical mutations are a heterogeneous group. Here, we examined tropomyosin-related kinase (TRK) fusion in GIST cases without KIT/PDGFRA mutations (KIT/PDGFRA wild-type (WT) GISTs). We retrospectively analyzed patients who were diagnosed with GISTs at the Yonsei Cancer Center, Severance Hospital, between January 1998 and December 2016. Thirty-one patients with KIT/PDGFRA WT GISTs were included in the analysis. TRK expression in tumor samples was assessed by pan-TRK immunohistochemistry (IHC), and the neurotrophic tyrosine receptor kinase (NTRK: the gene encoding TRK) rearrangement was analyzed by fluorescence in situ hybridization (FISH). IHC analyses revealed that five cases in this cohort exhibited a weak to moderate TRK expression. NTRK1 fusions were detected in three tumor samples, and two samples harbored NTRK3 fusions. The remaining 26 samples did not harbor NTRK fusions. Two types of NTRK fusions were detected, and the overall NTRK fusion frequency in KIT/PDGFRA WT GIST cases was 16% (5/31). Our data provide insights into the molecular alterations underpinning KIT/PDGFRA WT GISTs. More effort should be devoted to improve methods to identify this distinct disease subtype within the KIT/PDGFRA WT GIST group.