Prevalence of neurotrophic tropomyosin receptor kinase (<scp>NTRK</scp>) fusion gene positivity in patients with solid tumors in Japan

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Members of the neurotrophic tropomyosin receptor kinase (<jats:italic>NTRK</jats:italic>) gene family, <jats:italic>NTRK1</jats:italic>, <jats:italic>NTRK2</jats:italic>, and <jats:italic>NTRK3</jats:italic> encode TRK receptor tyrosine kinases. Intra‐ or inter‐chromosomal gene rearrangements produce <jats:italic>NTRK</jats:italic> gene fusions encoding fusion proteins which are oncogenic drivers in various solid tumors.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>This study investigated the prevalence of <jats:italic>NTRK</jats:italic> fusion genes and identified fusion partners in Japanese patients with solid tumors recorded in the Center for Cancer Genomics and Advanced Therapeutics database of comprehensive genomic profiling test.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>In the analysis population (<jats:italic>n</jats:italic> = 46,621), <jats:italic>NTRK</jats:italic> fusion genes were detected in 91 patients (0.20%). The rate was higher in pediatric cases (<18 years; 1.69%) than in adults (0.16%). <jats:italic>NTRK</jats:italic> gene fusions were identified in 21 different solid tumor types involving 38 different partner genes including 22 (57.9%) previously unreported <jats:italic>NTRK</jats:italic> gene fusions. The highest frequency of <jats:italic>NTRK</jats:italic> gene fusions was head and neck cancer (1.31%) and thyroid cancer (1.31%), followed by soft tissue sarcoma (STS; 0.91%). A total of 97 <jats:italic>NTRK</jats:italic> fusion gene partners were analyzed involving mainly <jats:italic>NTRK1</jats:italic> (49.5%) or <jats:italic>NTRK3</jats:italic> (44.2%) gene fusions. The only fusion gene detected in head and neck cancer was <jats:italic>ETV6::NTRK3</jats:italic> (<jats:italic>n</jats:italic> = 22); in STS, <jats:italic>ETV6::NTRK3</jats:italic> (<jats:italic>n</jats:italic> = 7) and <jats:italic>LMNA::NTRK1</jats:italic> (n = 5) were common. Statistically significant mutual exclusivity of <jats:italic>NTRK</jats:italic> fusions with alterations was confirmed in <jats:italic>TP53</jats:italic>, <jats:italic>KRAS</jats:italic>, and <jats:italic>APC</jats:italic>. <jats:italic>NTRK</jats:italic> gene fusion was detected from 11 STS cases: seven unclassified sarcoma, three sarcoma NOS, and one Ewing sarcoma.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p><jats:italic>NTRK</jats:italic> gene fusion identification in solid tumors enables accurate diagnosis and potential TRK inhibitor therapy.</jats:p></jats:sec>