start-ver=1.4
cd-journal=joma
no-vol=13
cd-vols=
no-issue=12
article-no=
start-page=e7351
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2024
dt-pub=20240625
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Prevalence of neurotrophic tropomyosin receptor kinase (NTRK) fusion gene positivity in patients with solid tumors in Japan
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Background: Members of the neurotrophic tropomyosin receptor kinase (NTRK) gene family, NTRK1, NTRK2, and NTRK3 encode TRK receptor tyrosine kinases. Intra- or inter-chromosomal gene rearrangements produce NTRK gene fusions encoding fusion proteins which are oncogenic drivers in various solid tumors. <br>
Methods: This study investigated the prevalence of NTRK 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. <br>
Results: In the analysis population (n = 46,621), NTRK 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%). NTRK gene fusions were identified in 21 different solid tumor types involving 38 different partner genes including 22 (57.9%) previously unreported NTRK gene fusions. The highest frequency of NTRK 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 NTRK fusion gene partners were analyzed involving mainly NTRK1 (49.5%) or NTRK3 (44.2%) gene fusions. The only fusion gene detected in head and neck cancer was ETV6::NTRK3 (n = 22); in STS, ETV6::NTRK3 (n = 7) and LMNA::NTRK1 (n = 5) were common. Statistically significant mutual exclusivity of NTRK fusions with alterations was confirmed in TP53, KRAS, and APC. NTRK gene fusion was detected from 11 STS cases: seven unclassified sarcoma, three sarcoma NOS, and one Ewing sarcoma. <br>
Conclusions: NTRK gene fusion identification in solid tumors enables accurate diagnosis and potential TRK inhibitor therapy.
en-copyright=
kn-copyright=

en-aut-name=NakataEiji
en-aut-sei=Nakata
en-aut-mei=Eiji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=OsoneTatsunori
en-aut-sei=Osone
en-aut-mei=Tatsunori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=OgawaToru
en-aut-sei=Ogawa
en-aut-mei=Toru
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=TaguchiTomoyuki
en-aut-sei=Taguchi
en-aut-mei=Tomoyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=HattoriKana
en-aut-sei=Hattori
en-aut-mei=Kana
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KohsakaShinji
en-aut-sei=Kohsaka
en-aut-mei=Shinji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

affil-num=1
en-affil=Department of Orthopedic Surgery,  Okayama University
kn-affil=

affil-num=2
en-affil=Faculty of Medicine, Dentistry and  Pharmaceutical Sciences, Okayama  University
kn-affil=

affil-num=3
en-affil=Medical Affairs & Pharmacovigilance,  Bayer Yakuhin, Ltd
kn-affil=

affil-num=4
en-affil=Medical Affairs & Pharmacovigilance,  Bayer Yakuhin, Ltd
kn-affil=

affil-num=5
en-affil=Medical Affairs & Pharmacovigilance,  Bayer Yakuhin, Ltd
kn-affil=

affil-num=6
en-affil=National Cancer Center Research  Institute
kn-affil=
en-keyword=comprehensive genomic profiling
kn-keyword=comprehensive genomic profiling
en-keyword=neurotrophic tropomyosin receptor kinase (NTRK) gene fusion
kn-keyword=neurotrophic tropomyosin receptor kinase (NTRK) gene fusion
en-keyword=next-generation sequencing
kn-keyword=next-generation sequencing
en-keyword=solid tumors
kn-keyword=solid tumors
END