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    BIOMARKER:

    EML4-NTRK3 fusion

    i
    Other names: NTRK3, TRKC, Neurotrophic tyrosine kinase, receptor, type 3, EML4, EMAP Like 4, Restrictedly Overexpressed Proliferation-Associated Protein, Echinoderm Microtubule-Associated Protein-Like 4, Echinoderm Microtubule Associated Protein Like 4, Ropp 120, C2orf2, EMAP-4, EMAPL4, ROPP120, ELP120
    Entrez ID:
    4916; 27436
    Related biomarkers:
    Expression
    Mutation
    Fusion
    Others
    3ms
    The oncogenic fusion protein EML4-NTRK3 requires three salt bridges for stability and biological activity. (PubMed, Heliyon)
    We also demonstrate that EML4-NTRK3 is localized in the cytoplasm and fails to associate with microtubules. These data suggest potential therapeutic strategies for Infantile Fibrosarcoma cases bearing EML4-NTRK3 fusion through inhibition of salt bridge interactions and disruption of multimerization.
    Journal
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    NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • EML4 (EMAP Like 4) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    NTRK3 fusion • EML4-NTRK3 fusion • NTRK3 translocation
    10ms
    A novel EML4-NTRK3 fusion in lung adenocarcinoma with dramatic response to entrectinib. (PubMed, J Cancer Res Ther)
    Despite the rare occurrence, these alterations have gained importance owing to approval of drugs like entrectinib and larotrectinib targeting the kinase domain of the gene. Detection of these rests on the use of conventional modalities like Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH); however, accurate characterization requires direct sequencing methods. We report an interesting case of an NTRK fusion-positive NSCLC, exhibiting good response to entrectinib.
    Journal
    |
    NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • EML4 (EMAP Like 4) • ETV6 (ETS Variant Transcription Factor 6) • SQSTM1 (Sequestosome 1) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    NTRK1 fusion • NTRK3 fusion • SQSTM1-NTRK1 fusion • EML4-NTRK3 fusion • NTRK positive • NTRK fusion
    |
    Vitrakvi (larotrectinib) • Rozlytrek (entrectinib)
    over1year
    GENOMIC PROFILING OF GYNAECOLOGICAL SARCOMAS: REPORT FROM THE AUSTRALIA-WIDE PRECISION ONCOLOGY PROGRAM (CTOS 2023)
    Pt with PEComa harbouring a BRCA2 mutation and high TMB (20.3 mut/Mb) was treated on a matched MoST trial of olaparib and durvalumab (ACTRN12617001000392), achieving a complete radiological response and remained progression free at 22.6 mo. Molecular characterization of GS through CGP may be prognostic and can also identify actionable alterations in small subsets of patients that can help delineate this heterogeneous group.
    Tumor mutational burden • PD(L)-1 Biomarker • PARP Biomarker • BRCA Biomarker
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    ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • EML4 (EMAP Like 4) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • ATRX (ATRX Chromatin Remodeler) • TSC2 (TSC complex subunit 2) • TIMP3 (TIMP Metallopeptidase Inhibitor 3)
    |
    TP53 mutation • BRCA2 mutation • TMB-H • NTRK3 fusion • PTEN mutation • ALK fusion • TSC2 mutation • EML4-NTRK3 fusion
    |
    FoundationOne® CDx • TruSight Oncology 500 Assay • TruSight Tumor 170 Assay
    |
    Lynparza (olaparib) • Imfinzi (durvalumab) • Vitrakvi (larotrectinib)
    over1year
    Real-world challenges in undertaking NTRK fusion testing in non-small cell lung cancer. (PubMed, J Thorac Dis)
    NTRK fusions in NSCLC are rare. This study highlights real world diagnostic challenges regarding NTRK testing, such as requirements of adequate tumor tissue and appropriate testing methodologies.
    Journal • Real-world evidence • PD(L)-1 Biomarker • IO biomarker • Real-world
    |
    EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • EML4 (EMAP Like 4) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    PD-L1 expression • EGFR mutation • PIK3CA mutation • NTRK3 fusion • MET amplification • MET mutation • PIK3CA E542K • PIK3CA E542 • EML4-NTRK3 fusion • NTRK expression • NTRK fusion
    2years
    NTRK3 gene fusion in an adult ganglioglioma: illustrative case. (PubMed, J Neurosurg Case Lessons)
    To our knowledge, this is the first report of an NTRK3 fusion, EML4-NTRK3, in an adult ganglioglioma, which is otherwise mostly associated with BRAF alterations and activation of the mitogen-activated protein kinase signaling pathway. Further studies are needed to elucidate the function of the resultant fusion protein and determine whether it may serve as a future therapeutic target.
    Journal
    |
    BRAF (B-raf proto-oncogene) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • EML4 (EMAP Like 4) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    NTRK3 fusion • EML4-NTRK3 fusion
    over2years
    EML4-NTRK3 Fusion Cervical Sarcoma: A Case Report and Literature Review. (PubMed, Front Med (Lausanne))
    We found that age and mitotic rate may be associated with recurrence or metastasis by univariate survival analysis. To draw more convincing conclusions, there is a need to establish an international database of rare cases and aggregate these sporadic cases.
    Review • Journal
    |
    NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • EML4 (EMAP Like 4) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    NTRK3 fusion • EML4-NTRK3 fusion • NTRK fusion
    3years
    Targeted DNA and RNA Sequencing of Soft Tissue Spindle Cell Tumors Reveals a Rare MET-TFG and a Novel PWWP2A-RET Gene Fusions as well as Additional Recurrent PIK3CA Point Mutations (USCAP 2022)
    Besides identifying several rare or novel kinase fusions genes, our analysis also revealed various additional mutations including recurrent PIK3CA point mutations. Although their significance is unknown, they might be responsible for progression of tumors with LG morphology (LNT, FTPH) into tumors with HG morphology and/or acquisition of a more aggressive biological potential. Targeted therapy is effective and significantly aids in successful treatment.
    BRAF (B-raf proto-oncogene) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • RET (Ret Proto-Oncogene) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • EML4 (EMAP Like 4) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • ETV6 (ETS Variant Transcription Factor 6) • CD34 (CD34 molecule) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • NTRK (Neurotrophic receptor tyrosine kinase) • WWP2 (WW Domain Containing E3 Ubiquitin Protein Ligase 2)
    |
    PIK3CA mutation • NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • RET fusion • ETV6-NTRK3 fusion • EML4-NTRK3 fusion • MAP3K1 mutation • KIT fusion
    |
    TruSight Oncology 500 Assay
    3years
    Molecular characterisation of pancreatic ductal adenocarcinoma with NTRK fusions and review of the literature. (PubMed, J Clin Pathol)
    NTRK fusions are rare; however, with emerging therapeutic options targeting these fusions, detection is vital. Reflex testing for KRAS mutations and subsequent RNA-based screening could help identify these cases in PDAC.
    Review • Journal • Tumor Mutational Burden
    |
    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • EML4 (EMAP Like 4) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • SMAD4 (SMAD family member 4) • KANK1 (KN Motif And Ankyrin Repeat Domains 1) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    TP53 mutation • KRAS mutation • NTRK3 fusion • CDKN2A mutation • EML4-NTRK3 fusion • NTRK3 positive • NTRK fusion
    over3years
    [VIRTUAL] Prevalence of NTRK1/2/3 fusions in dMMR/MSI metastatic colorectal cancer (ESMO 2021)
    Frequency of NTRK1/2/3 fusions was 5.8% in our dMMR/MSI mCRCs cohort. These fusions were not restricted to sporadic cases. The diagnostic accuracy of pan-TRK IHC was low.
    IO biomarker
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • MSI (Microsatellite instability) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • EML4 (EMAP Like 4) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • ETV6 (ETS Variant Transcription Factor 6) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • TPM3 (Tropomyosin 3) • LMNA (Lamin A/C) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    BRAF V600E • KRAS mutation • MSI-H/dMMR • BRAF V600 • NTRK1 fusion • NTRK3 fusion • NTRK2 fusion • MSH2 mutation • EML4-NTRK3 fusion • NTRK positive • MSH6 expression • NTRK fusion
    |
    Archer® FusionPlex® Lung Kit • VENTANA pan-TRK (EPR17341) Assay