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Updated: Jul 18, 2026
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
A novel EML4-NTRK3 fusion in lung adenocarcinoma with dramatic response to entrectinib
Ullas Batra1, Shrinidhi Nathany1, Mansi Sharma1
1Department of Medical Oncology, Section of Molecular Diagnostics, Pathology, Rajiv Gandhi Cancer Institute and Research Centre, Delhi, India.
Abstract:
In-frame fusions in NTRK genes, with intact kinase domain, have been reported to occur at higher frequencies in rare tumors like infantile fibrosarcoma, congenital mesoblastic nephroma, and secretory carcinoma, whereas they occur at very low frequencies in common malignancies like NSCLC and colon cancers (0.1%-1%). 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. More than 50 fusion partners have been described, and only in-frame fusions result in constitutive ligand-independent kinase activity leading to oncogenesis. The commonly reported NTRK fusions in the lung include SQSTM1-NTRK1, ETV6-NTRK3, and SQSTM1-NTRK3. 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.
Insights
NTRK gene fusions, though rare in non-small cell lung cancer (NSCLC), drive oncogenesis and respond to targeted therapies like entrectinib. This case highlights successful treatment of NTRK fusion-positive NSCLC.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Neurotrophic tyrosine receptor kinase (NTRK) gene fusions are oncogenic drivers found in rare tumors and less frequently in common malignancies like non-small cell lung cancer (NSCLC).
- Targeted therapies, including entrectinib and larotrectinib, are approved for NTRK fusion-positive cancers, targeting the intact kinase domain crucial for oncogenesis.
- Over 50 fusion partners exist, with in-frame fusions leading to constitutive kinase activity; common lung fusions include SQSTM1-NTRK1, ETV6-NTRK3, and SQSTM1-NTRK3.
Observation:
- Conventional detection methods like Immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) are used, but direct sequencing is required for accurate characterization.
- This report details a case of non-small cell lung cancer (NSCLC) positive for an NTRK fusion.
Findings:
- The identified NTRK fusion in NSCLC was accurately characterized using direct sequencing methods.
- The patient's non-small cell lung cancer (NSCLC) exhibited a positive response to entrectinib therapy.
Implications:
- NTRK fusions represent actionable targets in NSCLC, even at low frequencies.
- Targeted therapy demonstrates efficacy in NTRK fusion-positive NSCLC, underscoring the importance of molecular profiling.
- Accurate detection through sequencing is vital for identifying patients who may benefit from specific therapies like entrectinib.
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