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Several challenges exist when testing for cancers for the presence of NTRK gene fusion. Each test methodology has advantages and disadvantages in terms of resource efficiency, turnaround time, sensitivity, and specificity which must be balanced with the individual case in mind. For example, NTRK3 FISH would be a good choice in patients where there is high suspicion of ETV6-NTRK3 fusion while RNA testing would be ideal to clarify cryptic NTRK gene rearrangements detected via DNA sequencing. In addition, there is some uncertainty regarding which patients should undergo testing for NTRK gene fusions.

To address these challenges, target enrichment strategies can be used to enhance the study population being tested for NTRK gene fusions [1-3]. Target enrichment allows for the rapid screening of a large patient population to identify a small percentage who have NTRK gene fusions. Target enrichment techniques such as IHC may be useful for more cases in which NTRK fusions are somewhat common, whereas NGS may be more suitable for rare diseases as other potential mutations could be identified. Another strategy would be to focus on tumour histologies or molecular subgroups with a higher likelihood of harbouring an NTRK gene fusion.

Further details on the methodology, advantages, disadvantages and applications in NTRK gene fusion detection methodology can be found by clicking on each method below.

References

  1. Hechtman JF, Benayed R, Hyman DM et al. Pan-Trk Immunohistochemistry Is an Efficient and Reliable Screen for the Detection of NTRK Fusions. Am J Surg Pathol 2017; 41: 1547-1551.
  2. Murphy DA, Ely HA, Shoemaker R et al. Detecting Gene Rearrangements in Patient Populations Through a 2-Step Diagnostic Test Comprised of Rapid IHC Enrichment Followed by Sensitive Next-Generation Sequencing. Appl Immunohistochem Mol Morphol 2017; 25: 513-523.
  3. Zheng Z, Liebers M, Zhelyazkova B et al. Anchored multiplex PCR for targeted next-generation sequencing. Nat Med 2014; 20: 1479-1484.

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