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

Eiji Nakata; Tatsunori Osone; Toru Ogawa; Tomoyuki Taguchi; Kana Hattori; Shinji Kohsaka

doi:10.1002/cam4.7351

journal article Open Access Jun 01, 2024

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

Eiji Nakata

Tatsunori Osone Toru Ogawa Tomoyuki Taguchi Kana Hattori Shinji Kohsaka

Cancer Medicine Vol. 13 No. 12 · Wiley

View at Publisher Save 10.1002/cam4.7351

Abstract

AbstractBackgroundMembers 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.MethodsThis 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.ResultsIn 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.ConclusionsNTRK gene fusion identification in solid tumors enables accurate diagnosis and potential TRK inhibitor therapy.

Topics

No keywords indexed for this article. Browse by subject →

References

35

[1]

10.1158/1078-0432.ccr-18-1156

[2]

10.3390/cancers10040105

[3]

10.1038/s41571-018-0113-0

[4]

10.1093/annonc/mdz383

[5]

10.1093/annonc/mdz384

[6]

10.1038/s41379-021-00913-8

[7]

10.1200/po.18.00183

[8]

10.1158/1078-0432.ccr-19-3165

[9]

10.1177/1758835920975613

[10]

10.1038/s41698-021-00206-y

[11]

10.1016/j.amsu.2022.103893

[12]

10.1016/j.cancergen.2021.11.006

[13]

10.1038/s41467-022-30496-0

[14]

10.1056/nejmoa1714448

[15]

10.1016/s1470-2045(19)30856-3

[16]

Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: integrated analysis of three phase 1–2 trials

Robert C Doebele, Alexander Drilon, Luis Paz-Ares et al.

The Lancet Oncology 10.1016/s1470-2045(19)30691-6

[17]

10.3390/ph14070632

[18]

10.1007/s10147-023-02345-7

[19]

C-CAT: The National Datacenter for Cancer Genomic Medicine in Japan

Takashi Kohno, Mamoru Kato, Shinji Kohsaka et al.

Cancer Discovery 10.1158/2159-8290.cd-22-0417

[20]

10.3390/life11080796

[21]

10.1371/journal.pone.0266112

[22]

10.1136/jclinpath-2018-205679

[23]

10.1016/j.jmoldx.2019.03.008

[24]

10.1093/annonc/mdx671.004

[25]

10.1038/s41598-021-85075-y

[26]

C‐CAT registration status. Accessed 17 August 2023.https://for‐patients.c‐cat.ncc.go.jp/registration_status/.

[27]

OncoTree: A Cancer Classification System for Precision Oncology

Ritika Kundra, Robert Sheridan, Sahussapont Joseph Sirintrapun et al.

JCO Clinical Cancer Informatics 10.1200/cci.20.00108

[28]

10.1136/bmj.39335.541782.ad

[29]

CONSORT 2010 Statement: updated guidelines for reporting parallel group randomised trials

K. F Schulz, D. G Altman, D. Moher

BMJ 10.1136/bmj.c332

[30]

10.1016/j.annonc.2020.08.2232

[31]

10.3390/diagnostics11030478

[32]

10.1002/cjp2.208

[33]

10.1016/j.cllc.2019.09.004

[34]

10.1002/gcc.23089

[35]

10.1097/pas.0b013e3181d9efcc

Metrics

15

Citations

35

References

Details

Published: Jun 01, 2024
Vol/Issue: 13(12)
License: View

Authors

E

Eiji Nakata

Department of Orthopedic Surgery Okayama University Okayama Japan; Center for Comprehensive Genomic Medicine Okayama University Hospital Okayama Japan

T

Tatsunori Osone

Faculty of Medicine, Dentistry and Pharmaceutical Sciences Okayama University Okayama Japan

T

Toru Ogawa

Medical Affairs & Pharmacovigilance Bayer Yakuhin, Ltd Osaka Japan

T

Tomoyuki Taguchi

Medical Affairs & Pharmacovigilance Bayer Yakuhin, Ltd Osaka Japan

K

Kana Hattori

Medical Affairs & Pharmacovigilance Bayer Yakuhin, Ltd Osaka Japan

S

Shinji Kohsaka

National Cancer Center Research Institute Tokyo Japan

Funding

Bayer Yakuhin

Cite This Article

Eiji Nakata, Tatsunori Osone, Toru Ogawa, et al. (2024). Prevalence of neurotrophic tropomyosin receptor kinase (NTRK) fusion gene positivity in patients with solid tumors in Japan. Cancer Medicine, 13(12). https://doi.org/10.1002/cam4.7351

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

You May Also Like