NTRK Fusions

NTRK fusion screening for cancer

Gene fusions are detected in 15% of metastatic cancers regardless of cancer tissue lineage. Kinase fusions make up 35% of known fusions¹ and have been targeted by several new therapies, including therapies for fusions with the neurotrophic tyrosine kinase genes (NTRK1, NTRK2, and NTRK3).

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Why NTRK fusions are important in cancer

The diversity and complexity of NTRK biology has increased with frequent discovery of new fusion partners. Targetable kinase fusions show response to tyrosine kinase inhibitor, regardless of the fusion partner.2 Because NTRK fusion partners can be missed by commercially available amplicon-based NTRK detection assays3-5, comprehensive assays that detect novel fusion partners can provide value.

70% of NTRK fusion partners can be missed by commercially available amplicon assays. 3-5

NGS-based detection of novel NTRK fusions

Next-generation sequencing (NGS) assays that query RNA using hybrid-capture chemistry can capture novel NTRK RNA fusions. Without a priori knowledge in primer design, unknown fusion partners can be captured and sequenced—leading to new biomarker discoveries.

chart showing difference between amplicon chemistry and rna-hybrid capture
Marjorin Liugtenberg

If you look at gene fusions there are more and more gene fusions that are important to know for the clinician — ALK, RET, RAS, NTRK, FGFR. Testing with an NGS approach allows you to test them all in one single reaction and you do not need additional tissue.

Marjolin Ligtenberg, PhD, Laboratory of Tumor Genetics, Radboud University Medical Center
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CGP enables analysis of RNA fusions of NTRK and many more genes in a single assay

The number of fusion-based biomarkers and targeted therapies in cancer are consistently increasing. Iterative testing for individual biomarkers can be challenging when time and sample are limiting. By consolidating relevant biomarkers into a single test, and using hybrid-capture chemistry to enable novel fusion detection, CGP can provide significant savings in sample, time, and cost.

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diagram showing translocation and gene fusion

Comprehensive NTRK fusion detection

RNA-based hybrid-capture NGS enables the capturing of more NTRK fusions than DNA sequencing alone, agnostic of the fusion partner. Learn how Illumina NGS technology detects more fusions, including NTRK fusions.

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NTRK fusion news and interviews

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Matching patients with rare genetic mutations to targeted therapy

The Illumina TruSight Oncology Comprehensive (EU) test enables targeted therapy with Bayer's VITRAKVI® (larotrectinib) for patients with NTRK fusion cancer.

vivek subbiah
Testing for fusions with Vivek Subbiah, MD

Vivek Subbiah, MD, explains how patients with rare and common tumors can benefit from next generation sequencing-based testing for NTRK gene fusions.

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Collaborating to evaluate the impact of in-house CGP to enhance patient care

Illumina and Allegheny Health Network to assess the efficacy of in-house testing for both tissue and blood samples and identify instances where blood-based testing is most beneficial.

  1. Zehir, et al. Mutational Landscape of Metastatic Cancer Revealed from Prospective Clinical Sequencing of 10,000 Patients Nat Med. 2017;23(6):703-713.
  2. Vitravki [package insert]. Stamford, CT: Loxo Oncology, Inc; November 2018.
  3. Hsiao SJ, Zehir A, Sireci AN, Aisner DL. Detection of tumor NTRK gene fusions to identify patients who may benefit from TRK inhibitor therapy. J Mol Diagn. 2019. doi: 10.1016/j.jmoldx.2019.03.008.
  4. OncomineTM Focus Assay, AmpliSeqTM Library page. https://www.thermofisher.com/order/catalog/product/A35957. Accessed February 14, 2019.
  5. St. James’s Hospital, Cancer Molecular Diagnostics Solid Tumour Service User Guide, http://www.stjames.ie/Departments/DepartmentsA-Z/C/CancerMolecularDiagnosticsLaboratory/DepartmentinDepth/User%20handbook%20v2.pdf. Accessed February 14, 2019.
  6. Cheng DT, Mitchell TN, Zehir A, et al. Memorial Sloan Kettering-Integrated Mutation Proling of Actionable Cancer Targets (MSK-IMPACT): A hybridization capture-based next-generation sequencing clinical assay for solid tumor molecular oncology. J Mol Diagn. 2015;17(3):251-264.