Prevalence of NTRK gene fusions in a large cohort of Japanese patients with lung cancer

Nakamura, Atsushi; Udagawa, Hibiki; Matsumoto, Shingo; Sugawara, Shunichi; Shingyoji, Masato; Horiike, Atsushi; Okamoto, Isamu; Hida, Toyoaki; Saeki, Sho; Ohe, Y.; Ogawara, Daiki; Kataoka, Yuki; Miyata, Yoshihiro; Mitsufuji, Hisashi; Kuyama, Shoichi; Kanemaru, Ryota; Kato, Terufumi; Hirata, Akira; Yoh, Kiyotaka; Goto, Kōichi

doi:10.1093/annonc/mdx671.004

Cited by 3 publications

(3 citation statements)

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“…Only one (0.04%) ETC6-NTRK3 fusion mutation was found in 2668 patients; NTRK1 and NTRK2 were not found. 9 In May 2017, Nature Medicine published a large-scale, prospective, clinical sequencing study using the MSK-IMPACT method at the Memorial Sloan Kettering Cancer Research Center. They performed more than 300 detailed tumor types in more than 10,000 patients with advanced cancer by NGS, including 10 cases NTRK1 fusion mutation, lung adenocarcinoma accounted for 0.13% (2/1563), and co-mutation with P2RY8 and VANGL2, respectively.…”

Section: Discussionmentioning

confidence: 99%

Analysis of NTRK mutation and clinicopathologic factors in lung cancer patients in northeast China

Yan

Liu

et al. 2020

Int J Biol Markers

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Objective: NTRK mutations and clinicopathological factors in patients with lung cancer in northeast China were analyzed by next-generation sequencing (NGS), and references were provided for patients with NTRK mutations undergoing targeted therapy in northeast China. Methods: A total of 224 specimens in 173 patients with lung cancer were collected. This included 51 patients with matched tissue and whole blood samples,133 tissue samples, 84 whole blood samples, and 7 pleural effusion samples. NGS (520 genes) was used to detected NTRK mutations and clinicopathologic factors. Results: NTRK mutation was detected in eight patients (8/173, 4.6%), including four NTRK missense mutations (4/173, 2.3%), two NTRK fusion gene mutations (2/173, 1.2%), and two NTRK copy number deletions (2/173, 1.2%). Among the eight patients with NTRK mutations, four were associated with lung cancer driver gene mutations (3/4 EGFR, 1/4ALK); NTRK in two patients was inconsistent in tissue and paired whole blood testing; NTRK missense mutation was detected in one patient, and NTRK copy number deletion was detected in the other; and NTRK wild type was detected in two patients. There was no correlation between NTRK mutation and clinicopathologic factors (including gender, age, pathological type, smoking status, metastasis site). Conclusion: NTRK mutation was only 4.6%, effective fusion gene mutation was 1.2%, and common driver gene mutation in lung cancer was evident in 50% of patients. The results of NTRK were inconsistent with matched tissues and whole blood. Therefore, patients with NTRK mutation should use a variety of specimen types and large target area sequencing (panel) analysis method to provide individualized treatment.

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Section: Discussionmentioning

confidence: 99%

Analysis of NTRK mutation and clinicopathologic factors in lung cancer patients in northeast China

Yan

Liu

et al. 2020

Int J Biol Markers

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“…First, NTRK fusion is a relatively rare molecular event in patients with lung adenocarcinomas from the East Asian population. Nakamura et al 36 from Japan reported that they only detected one NTRK fusion (ETV6-NTRK3) in 2088 non-squamous lung cancers. Second, we used surgically resected samples for fusion detection in this study (mostly at early stage), whereas other reports may have used biopsy tissues (mostly at advanced stage).…”

Section: Discussionmentioning

confidence: 99%

Detection of Novel NRG1, EGFR, and MET Fusions in Lung Adenocarcinomas in the Chinese Population

Pan

Zhang

et al. 2019

Journal of Thoracic Oncology

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Introduction: Multiple oncogene fusions beyond ALK receptor tyrosine kinase (ALK), RET, and ROS1 fusion has been described in lung cancer, especially in lung adenocarcinomas without common oncogenic mutations. Molecular inhibitors have been developed and proved effective for patients whose tumors harbor these novel alterations. Methods: A consecutive series of surgically resected lung adenocarcinomas were collected and profiled using an enrichment strategy to detect nine common oncogenic driver mutations and fusions concerning EGFR, KRAS, HER2, BRAF, MET, ALK, RET, ROS1, and FGFR. Driver-negative cases were further analyzed by a comprehensive RNA-based nextgeneration sequencing (NGS) fusion assay for novel fusions. Results: In total, we profiled 1681 lung adenocarcinomas, among which 255 cases were common driver-negative. One hundred seventy-seven cases had sufficient tissue for NGS fusions screening, which identified eight novel fusions. NRG1 fusions occurred in 0.36% of all lung adenocarcinoma cases (6 of 1681 cases), including 4 CD74-NRG1-positive cases, 1 RBPMS-NRG1-positive case, and 1 novel ITGB1-NRG1-positive case. Furthermore, another 2 novel fusions were also detected, including 1 EGFR-SHC1 fusion and 1 CD47-MET fusion, both of which were in-frame and retained the functional domain of the corresponding kinases. No fusion event was detected for NTRK, KRAS, BRAF or HER2 genes in this cohort. Detailed clinicopathologic data showed that invasive mucous adenocarcinoma (three of eight cases) and acinar-predominant adenocarcinoma (three of eight cases) were the most prevalent pathologic subtypes among novel fusions. Conclusions: Fusions affecting NRG1, EGFR, and MET were detected in 0.48% of unselected lung adenocarcinomas, and NRG1 fusions ranked the most prevalent fusions in common driver-negative lung adenocarcinomas from Chinese population. RNA-based NGS fusion assay was an optional method for screening actionable fusions in common driver-negative cases.

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“…Furthermore, no real‐world cross‐sectional studies of NTRK fusion genes by cancer type in Asia have been conducted. Previous large scale NTRK fusion gene testing studies in Japan, have focused on patients with lung cancer 24 or colorectal adenocarcinomas. 25 This is the first study which analyses NTRK fusion genes in multiple solid tumors in Asian patients.…”

Section: Introductionmentioning

confidence: 99%

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

Nakata,

Osone,

Ogawa

et al. 2024

Cancer Medicine

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BackgroundMembers 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.

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Prevalence of NTRK gene fusions in a large cohort of Japanese patients with lung cancer

Cited by 3 publications

References 0 publications

Analysis of NTRK mutation and clinicopathologic factors in lung cancer patients in northeast China

Analysis of NTRK mutation and clinicopathologic factors in lung cancer patients in northeast China

Detection of Novel NRG1, EGFR, and MET Fusions in Lung Adenocarcinomas in the Chinese Population

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

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