Tropomyosin-Related Kinase Fusions in Gastrointestinal Stromal Tumors

The canonical mutations in gastrointestinal stromal tumors (GISTs) are typically activating mutations in 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 mutations ( 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 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 ( : 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. fusions were detected in three tumor samples, and two samples harbored fusions. The remaining 26 samples did not harbor fusions. Two types of fusions were detected, and the overall fusion frequency in WT GIST cases was 16% (5/31). Our data provide insights into the molecular alterations underpinning WT GISTs. More effort should be devoted to improve methods to identify this distinct disease subtype within the WT GIST group.