Some cases of gastrointestinal stromal tumor (GIST) without mutations in the typical KIT or PDGFRA genes (KIT/PDGFRA WT) may contain tropomyosin-related kinase (TRK) fusions, according to a study published in Cancers.

A total of 16% of GIST cases (5/31) were found to contain TRK fusions in the neurotrophic tyrosine receptor kinase (NTRK) gene, which encodes TRK molecules, at a single clinical site during the study. These fusions included 3 cases of fusion in the NTRK1 gene and 2 in the NTRK3 gene.

The identification of GIST cases with TRK fusions is important, as the primary treatment for GIST, imatinib, has a lower response rate in KIT/PDGFRA WT cases. First-generation TRK inhibitors, including larotrectinib and entrectinib, have been found to have antitumor activity in a variety of TRK-fusion positive cancers, however. Identification of GIST patients who may benefit from this type of treatment is important to improve therapeutic outcomes.


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“Our results provided insights into the molecular alterations underpinning KIT/PDGFRA WT GISTs. Although KIT/PDGFRA WT GISTs are rare, our clinical predictions could aid physicians in identifying patients eligible for NTRK fusion screening and therapeutic targeting,” the authors said.

Read more about GIST etiology.

A total of 821 patients were diagnosed with GISTs between January 1998 and December 2016 at the Yonsei Cancer Center in Seoul, Korea. Of the 821 patients, 38 did not have KIT/PDGFRA mutations but only 31 had intact samples available for analysis. NTRK fusions were identified in 5 of the 31 patient samples.

NTRK fusions were detected through fluorescence in situ hybridization (FISH) and immunohistochemistry analysis. Of the 5 patients detected with fusions, all underwent curative resection surgery. Disease recurrence occurred in only 2 out of the 5 patients. Three of the patients received imatinib treatment as either adjuvant therapy after resection or palliative care following disease recurrence.

Reference

Lee JH, Shin SJ, Choe EA, et al. Tropomyosin-related kinase fusions in gastrointestinal stromal tumors. Cancers. 2022;14(11):2659. doi:10.3390/cancers14112659