NTRK Fusion Gene Detection Kit

* Includes all controls

Fusion Genes in Lung Cancer

The NTRK1, NTRK2 and NTRK3 genes encode TrkA, TrkB and TrkC, respectively, which are members of the Trk receptor family.

The Trk receptors contain an extracellular domain for ligand binding, a transmembrane domain, and an intracellular region with a kinase domain. Most Trk signal transduction pathways are mediated by ligand binding that stimulates oligomerization of the receptors and phosphorylation of specific tyrosine residues in the intracytoplasmic kinase domain, regulating proliferation, differentiation and survival in normal cells.

Chromosomal rearrangement produces oncogenic Trk fusions that contain a 3’ region of the NTRK gene joined with a 5’ sequence of a fusion gene partner. The promoter region of the 5’ partner drives the expression of the fusion transcript, which encodes an in-frame protein comprising the N-terminus of the 5’ fusion partner and the C-terminal tyrosine kinase domain of the Trk receptor. The fusion proteins lack the extracellular ligand binding domain of the full-length Trk protein and typically contain one or more dimerization domains from the 5’ partner. Gene fusions involving NTRK1, NTRK2, or NTRK3 have been found as oncogenic drivers in multiple solid tumors, and are responsible for the initiation and maintenance of the cancer.

Common tumor types, such as lung cancer, colorectal cancer and melanoma harbor NTRK fusions at a low frequency, typically ranging from 0.1% to 2%, while rare tumor types, such as secretory breast cancer, secretory carcinoma of the salivary gland, and infantile fibrosarcoma display NTRK fusions at a high frequency of >75% (Hsiao et al., 2019).

Small molecule inhibitors of Trk tyrosine kinases have demonstrated rapid and durable responses in patients with Trk fusion-positive solid tumors. The first-generation TRK inhibitor, Entrectinib, which is a pan-Trk, ROS1 and ALK inhibitor, functions as an ATP competitor to inhibit Trk receptor tyrosine kinase activity. Analysis of three phase I/II clinical trials demonstrated that median duration of response was 20.0 months, and median progression-free survival was 13.8 months (Demetri et al., 2022).

Kit Features

The NTRK Fusion Gene Detection Kit provides reagents for detecting NTRK1, NTRK2, and NTRK3 fusion genes in human RNA isolated from solid tumors.

The one-step assay combines first-strand cDNA synthesis (reverse transcription) and subsequent amplification of mutant and reference genes, minimizing hands-on time and reducing the risk of introducing contaminants during the workflow. The kit detects a total of 66 variants in 8 reactions.

This kit is compatible with various sample types and can be used to detect mutations in RNA isolated from fresh-frozen and formalin-fixed paraffin-embedded (FFPE) tissue samples.

Equipment & Materials

The NTRK Fusion Gene Detection Kit requires a real-time PCR instrument capable of detecting FAM and VIC fluorescent probes. This kit includes primer/probe mix for detection of all variants mentioned above, one-step enzyme mix for cDNA synthesis and PCR detection, as well as validated controls. Columns and reagents for RNA isolation are not included.