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BIOMARKER:

LMNA-NTRK1 fusion

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Other names: LMNA, Prelamin-A/C, LMN1, Mandibuloacral dysplasia type A, Limb girdle muscular dystrophy 1B (autosomal dominant), Cardiomyopathy dilated 1A (autosomal dominant), Lamin A/C, FPLD2, LGMD1B, CMT2B1, Renal carcinoma antigen NY-REN-32, Progeria 1 (hutchinson-gilford type), NTRK1, MTC, TRK, TRKA, Neurotrophic tyrosine kinase, receptor, type 1
Entrez ID:
5ms
Gene fusions and oncogenic mutations in MLH1 deficient and BRAFV600E wild-type colorectal cancers. (PubMed, Virchows Arch)
"Our results show that kinase fusions (20/30, 67%) and most importantly targetable NTRK1 fusions (7/30, 23%) are frequent in CRCs with dMLH1/BRAFV600Ewt/MLH1ph/RASwt. NGS was the most comprehensive method in finding the fusions, of which a subset can be screened by Idylla or IHC, provided that the result is confirmed by NGS."
Journal
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BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • RET (Ret Proto-Oncogene) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • MLH1 (MutL homolog 1) • TPM3 (Tropomyosin 3) • LMNA (Lamin A/C)
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BRAF V600E • BRAF V600 • NTRK1 fusion • RET fusion • ALK rearrangement • ALK fusion • BRAF wild-type • BRAF fusion • TPM3-NTRK1 fusion • LMNA-NTRK1 fusion • MLH1 mutation • NTRK expression
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Idylla™ GeneFusion Assay • Archer® FusionPlex® Lung Kit • VENTANA pan-TRK (EPR17341) Assay
5ms
Primary NTRK-rearranged Spindle Cell Neoplasm of the Lung: A Clinicopathologic and Molecular Analysis of 3 Cases. (PubMed, Am J Surg Pathol)
All 3 patients are alive without the disease (median follow-up, 9 mo; range, 4 to 87 mo). The cases present herein demonstrate that NTRK-rearranged spindle cell neoplasms may occur primarily in the lung, albeit extremely rare, and should be included in the differential diagnosis of primary pulmonary spindle cell neoplasms.
Journal
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ALK (Anaplastic lymphoma kinase) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • TPM3 (Tropomyosin 3) • CD34 (CD34 molecule) • LMNA (Lamin A/C) • SOX10 (SRY-Box 10) • NTRK (Neurotrophic receptor tyrosine kinase) • STAT6 (Signal transducer and activator of transcription 6)
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NTRK1 fusion • TPM3-NTRK1 fusion • LMNA-NTRK1 fusion
8ms
Clinicopathologic Spectrum of NTRK fusion-positive Tumors Detected by Clinical RNA Sequencing Panel (USCAP 2022)
NTRK fusion-positive entities presented with a wide clinical and histologic spectrum, in a third of which the finding was unexpected. Uncommon/novel NTRK fusions may be present in classic entities negative for canonical fusions by targeted testing and comprehensive fusion detection should be pursued in such cases. Positivity for pan-TRK IHC, diffuse or focal, may be helpful in uncommon clinical presentations.
Clinical
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NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • ETV6 (ETS Variant Transcription Factor 6) • TPM3 (Tropomyosin 3) • LMNA (Lamin A/C) • KANK1 (KN Motif And Ankyrin Repeat Domains 1) • NTRK (Neurotrophic receptor tyrosine kinase)
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NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • ETV6-NTRK3 fusion • TPM3-NTRK1 fusion • LMNA-NTRK1 fusion • NTRK positive • NTRK fusion
9ms
[VIRTUAL] CANTRK: A Canadian Ring Study to Optimize Detection of NTRK Gene Fusions by Next-Generation Sequencing (NGS) (AMP 2021)
The CANTRK study demonstrated a high level of agreement in detection of NTRK fusions by NGS RNA testing across different NGS panels. Fusions not detected by certain panels were due either to absence of targets in amplicon primer panels, or potential bioinformatic challenges. Issues encountered during the study, such as defining quality criteria for reporting a positive result, types of results requiring confirmation, and reporting requirements, will be used to formulate a best practice guideline for analysis and reporting of gene fusions detected by NGS methods.
Next-generation sequencing
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ALK (Anaplastic lymphoma kinase) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • ETV6 (ETS Variant Transcription Factor 6) • TPM3 (Tropomyosin 3) • LMNA (Lamin A/C) • NTRK (Neurotrophic receptor tyrosine kinase)
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NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • ALK fusion • ETV6-NTRK3 fusion • ROS1 fusion • TPM3-NTRK1 fusion • LMNA-NTRK1 fusion • ALK-ROS1 fusion • NTRK fusion
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Oncomine™ Comprehensive Assay v3M • Archer® FusionPlex® Lung Kit • Oncomine Focus Assay • Oncomine Precision Assay
9ms
PBI-200: in vivo efficacy of a novel, highly CNS-penetrant next generation TRK inhibitor (SNO 2021)
A BaF3 xenograft model encoding the LMNA-NTRK1 gene fusion and G595R solvent front mutation showed superior efficacy with PBI-200 relative to first-generation compounds larotrectinib and entrectinib, and equivalent efficacy to the second-generation compound selitrectinib, in terms of tumor growth inhibition. Together, these data suggest that PBI-200 has potential as a best-in-class, highly CNS-penetrant next generation TRKi. A Phase 1/2 clinical trial evaluating PBI-200 in NTRK fusion-positive patients, including patients with PBT, is ongoing (NCT04901806).
Preclinical
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NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • LMNA (Lamin A/C) • NTRK (Neurotrophic receptor tyrosine kinase)
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NTRK1 fusion • LMNA-NTRK1 fusion • NTRK positive • NTRK1 G595R • NTRK fusion
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Vitrakvi (larotrectinib) • Rozlytrek (entrectinib) • selitrectinib (BAY 2731954) • PBI-200
12ms
NTRK oncogenic fusions are exclusively associated with the serrated neoplasia pathway in the colorectum and begin to occur in sessile serrated lesions. (PubMed, J Pathol)
NTRK fusions were detected only in SSLs of patients aged ?50?years, whereas BRAF mutation was found in younger age-onset SSLs. In conclusion, NTRK-rearranged colorectal tumors develop exclusively through the serrated neoplasia pathway and can be initiated from non-dysplastic SSLs without BRAF/KRAS mutations prior to full occurrence of MSI-high/CIMP-high.
Journal • MSi-H Biomarker
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BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • MSI (Microsatellite instability) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • EML4 (EMAP Like 4) • ETV6 (ETS Variant Transcription Factor 6) • MLH1 (MutL homolog 1) • TPM3 (Tropomyosin 3) • LMNA (Lamin A/C) • NTRK (Neurotrophic receptor tyrosine kinase)
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MSI-H/dMMR • BRAF mutation • NTRK1 fusion • NTRK3 fusion • TPM3-NTRK1 fusion • LMNA-NTRK1 fusion • NTRK fusion
1year
[VIRTUAL] Genomic Testing Approaches Used to Identify Neurotrophic Tyrosine Receptor Kinase (NTRK) Gene Fusions for Patient Enrollment in Clinical Trials of Larotrectinib (ECP 2021)
NTRK gene fusions occur with many partners with the majority occurring at a low frequency across multiple tumour types, supporting the need for validated and appropriate testing methodologies that work agnostic of 5’ partners.
Clinical
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NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • ETV6 (ETS Variant Transcription Factor 6) • TPM3 (Tropomyosin 3) • LMNA (Lamin A/C) • NTRK (Neurotrophic receptor tyrosine kinase)
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NTRK1 fusion • NTRK3 fusion • ETV6-NTRK3 fusion • TPM3-NTRK1 fusion • LMNA-NTRK1 fusion • NTRK fusion
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Vitrakvi (larotrectinib)
over1year
NTRK fusion-positive colorectal cancer in Japanese population. (PubMed, Pathol Int)
Both NTRK1 fusion-positive cases lacked activating mutations in KRAS and BRAF and were mismatch repair-deficient with loss of MLH1 and PMS2 expression and MLH1 promoter methylation. Our results show that receptor tyrosine kinase fusions are rare but present in colorectal cancers in Japanese patients, with a prevalence similar to that reported in other countries.
Clinical • Journal
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BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • MLH1 (MutL homolog 1) • PMS2 (PMS1 protein homolog 2) • TPM3 (Tropomyosin 3) • LMNA (Lamin A/C) • NTRK (Neurotrophic receptor tyrosine kinase)
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KRAS mutation • MSI-H/dMMR • BRAF mutation • NTRK1 fusion • ALK positive • ROS1 positive • ROS1 fusion • TPM3-NTRK1 fusion • LMNA-NTRK1 fusion • PMS2 mutation • NTRK1 positive • NTRK positive • NTRK fusion
over1year
Enrichment of Kinase Fusions in ESR1 Wild Type, Metastatic Breast Cancer Revealed by a Systematic Analysis of 4,854 Patients. (PubMed, Ann Oncol)
Kinase fusions in breast cancers are extremely rare, and appear to be enriched in hormone-resistant, metastatic carcinomas and mutually exclusive with ESR1 mutations. The present study expands the spectrum of genetic alterations activating MAPK signaling that can substitute for ESR1 mutations in this setting. Molecular testing at progression after endocrine therapy should include fusion testing, particularly in the absence of ESR1 hotspot alterations, in an effort to identify additional therapeutic options which may provide substantial clinical benefit.
Clinical • Journal
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HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • ER (Estrogen receptor) • FGFR2 (Fibroblast growth factor receptor 2) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • FGFR3 (Fibroblast growth factor receptor 3) • FGFR1 (Fibroblast growth factor receptor 1) • LMNA (Lamin A/C)
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NTRK1 fusion • ER mutation • FGFR2 fusion • FGFR fusion • FGFR1 fusion • FGFR3 fusion • LMNA-NTRK1 fusion
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Vitrakvi (larotrectinib)
over1year
[VIRTUAL] Use of pan-TRK immunohistochemistry for identification of NTRK fusions in mesenchymal neoplasms – real life experience (ECP 2020)
Pan-TRK (clone EPR17341, Roche/Ventana) immunhistochemistry is a reliable, highly sensitive but less specific diagnostic marker that can be expressed in non-NTRK-rearranged mesenchymal neoplasms. Conclusion Pan-TRK (clone EPR17341, Roche/Ventana) can be used as a surrogate marker for an identification of NTRK fusion, nevertheless, an RNA-based NGS for detection of the specific fusion should be performed to confirm the rearrangement if patients are undergoing targeted therapy.
Clinical
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NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • ETV6 (ETS Variant Transcription Factor 6) • LMNA (Lamin A/C) • NTRK (Neurotrophic receptor tyrosine kinase)
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NTRK1 fusion • LMNA-NTRK1 fusion • NTRK expression • NTRK fusion
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VENTANA pan-TRK (EPR17341) Assay
over1year
[VIRTUAL] Use of pan-TRK immunohistochemistry for identification of NTRK fusions in mesenchymal neoplasms – real life experience (ECP 2020)
Pan-TRK (clone EPR17341, Roche/Ventana) immunhistochemistry is a reliable, highly sensitive but less specific diagnostic marker that can be expressed in non-NTRK-rearranged mesenchymal neoplasms. Conclusion Pan-TRK (clone EPR17341, Roche/Ventana) can be used as a surrogate marker for an identification of NTRK fusion, nevertheless, an RNA-based NGS for detection of the specific fusion should be performed to confirm the rearrangement if patients are undergoing targeted therapy.
Clinical
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NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • ETV6 (ETS Variant Transcription Factor 6) • LMNA (Lamin A/C) • NTRK (Neurotrophic receptor tyrosine kinase)
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NTRK1 fusion • LMNA-NTRK1 fusion • NTRK expression • NTRK fusion
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VENTANA pan-TRK (EPR17341) Assay
over1year
[VIRTUAL] Use of pan-TRK immunohistochemistry for identification of NTRK fusions in mesenchymal neoplasms – real life experience (ECP 2020)
Pan-TRK (clone EPR17341, Roche/Ventana) immunhistochemistry is a reliable, highly sensitive but less specific diagnostic marker that can be expressed in non-NTRK-rearranged mesenchymal neoplasms. Conclusion Pan-TRK (clone EPR17341, Roche/Ventana) can be used as a surrogate marker for an identification of NTRK fusion, nevertheless, an RNA-based NGS for detection of the specific fusion should be performed to confirm the rearrangement if patients are undergoing targeted therapy.
Clinical
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NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • ETV6 (ETS Variant Transcription Factor 6) • LMNA (Lamin A/C) • NTRK (Neurotrophic receptor tyrosine kinase)
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NTRK1 fusion • LMNA-NTRK1 fusion • NTRK expression • NTRK fusion
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VENTANA pan-TRK (EPR17341) Assay
almost2years
[VIRTUAL] Rare Case of Lipofibromatosis-Like Neural Tumor in a 50-Year-Old Man (CAP 2020)
Histologic examination revealed a spindle cell neoplasm with fascicular proliferation of relatively plump, bland, fibroblastic to somewhat neural-appearing cells growing in an infiltrative fashion through the preexisting connective tissue (Figure 212, B and C). Immunohistochemistry showed coexpression of S100 protein, CD34, and TRK, and the lesion was found to be positive for the LMNA-NTRK1 fusion by next-generation sequencing.
Clinical
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NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • CD34 (CD34 molecule) • LMNA (Lamin A/C)
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NTRK1 fusion • LMNA-NTRK1 fusion
almost2years
Clinicopathological findings of pediatric NTRK fusion mesenchymal tumors. (PubMed, Diagn Pathol)
All cases of NTRK1 and NTRK3 fusion-positive pediatric tumors robustly expressed the Trk protein. A Trk immunopositive pattern and CD34/S100/nestin/CD10/SMA immunohistochemical expression may suggest the presence of NTRK fusion partner genes. LMNA-NTRK1 fusion sarcoma might be a low-grade subtype of infantile fibrosarcoma. Interestingly, more than half of the infantile fibrosarcoma cases were positive for S100 protein and CD10. The follow-up period of TPR-NTRK1 and LMNA-NTRK1 fusion-positive tumors are not enough to predict prognosis. However, ETV6-NTRK3 fusion-positive infantile fibrosarcomas showed an excellent prognosis with no evidence of disease for an average of 11.7 years, after gross total resection of the tumor.
Clinical • Journal
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NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • ETV6 (ETS Variant Transcription Factor 6) • CD34 (CD34 molecule) • LMNA (Lamin A/C) • NTRK (Neurotrophic receptor tyrosine kinase)
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NTRK1 fusion • NTRK3 fusion • ETV6-NTRK3 fusion • LMNA-NTRK1 fusion • NTRK1 positive • NTRK3 positive • NTRK positive • TPR-NTRK1 fusion • NTRK expression • NTRK fusion
almost2years
Broadening the spectrum of NTRK rearranged mesenchymal tumors and usefulness of pan-TRK immunohistochemistry for identification of NTRK fusions. (PubMed, Mod Pathol)
"It can be used as a surrogate marker for identification of NTRK fusion, nevertheless, an RNA-based NGS for detection of the specific fusion should be performed to confirm the rearrangement, if patients are undergoing targeted therapy. Additionally, we identified NTRK-fusion-positive, primary mesenchymal tumors of the lung and the skin."
Journal
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NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • ETV6 (ETS Variant Transcription Factor 6) • LMNA (Lamin A/C) • NTRK (Neurotrophic receptor tyrosine kinase)
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NTRK1 fusion • NTRK2 fusion • LMNA-NTRK1 fusion • NTRK positive • NTRK expression • NTRK fusion
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VENTANA pan-TRK (EPR17341) Assay
2years
[VIRTUAL] Neurotrophin tyrosine receptor kinase (NTRK) partners identified by next-generation sequencing in Chinese patients with solid tumours (ESMO 2020)
More than 20 different fusion partner genes of NTRK have been reported and most of these NTRK fusions respond well to NTRK inhibitors larotrectinib and/or entrectinib. Legal entity responsible for the study: The authors. Funding: Has not received any funding.
Clinical • Next-generation sequencing
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NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • CD74 (CD74 Molecule) • ETV6 (ETS Variant Transcription Factor 6) • LMNA (Lamin A/C) • NTRK (Neurotrophic receptor tyrosine kinase)
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NTRK1 fusion • LMNA-NTRK1 fusion • NTRK fusion
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Vitrakvi (larotrectinib) • Rozlytrek (entrectinib)
2years
[VIRTUAL] Large-scale study of NTRK fusions in Chinese solid tumors and using next generation sequencing: A multicenter study (AACR-II 2020)
TRK inhibitors such as LOXO-101, entrectinib, X396, AB-106, TL118 had remarkable and durable antitumor activities in patients (pts) with TRK fusion-positive cancers, regardless of age or tumor type. NTRK fusions are a rare molecular subtype in Chinese solid tumors. The NTRK gene fusions more commonly occurred in NSCLC (0.3%), CRC (0.4%) and BC (0.2%), and may occur without other targetable alterations such as EGFR, ALK, ROS1. The clinical evidence for responsiveness of NTRK fusions driven solid tumors provides an opportunity to personalize treatments and improve clinical outcomes for patients (pts).
Clinical • Next-generation sequencing
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EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • ETV6 (ETS Variant Transcription Factor 6) • TPM3 (Tropomyosin 3) • LMNA (Lamin A/C) • SQSTM1 (Sequestosome 1) • ESRP1 (Epithelial Splicing Regulatory Protein 1) • NTRK (Neurotrophic receptor tyrosine kinase)
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NTRK1 fusion • NTRK2 fusion • ETV6-NTRK3 fusion • TPM3-NTRK1 fusion • LMNA-NTRK1 fusion • NTRK fusion
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Vitrakvi (larotrectinib) • Rozlytrek (entrectinib) • Ensacove (ensartinib) • taletrectinib (AB-106) • Hamsa-1 (TL-118)