NTRK

IHC • FISH • NGS

Make NTRK gene fusion testing part of your patient care.

There are various methodologies to test for neurotrophic tropomyosin receptor kinase (NTRK) gene fusion, including immunohistochemistry (IHC), FISH, and RNA Fusion by next-generation sequencing (NGS).

Testing for NTRK gene fusions is essential to identify patients that harbor the genomic alterations who are now eligible for therapy that may ultimately address their cancer. It has been shown that patients with tumors driven by these gene rearrangements are excellent candidates for targeted tyrosine kinase receptor (TRK) inhibitors for locally advanced or metastatic solid tumors with NTRK fusions.

NTRK cancer types

NTRK gene fusion frequency1

NTRK gene fusions are a class of oncogenes associated with a wide range of pediatric and adult solid tumors.2 These genomic alterations may lead to TRK fusion proteins that are mutually exclusive oncogenic drivers that have been associated with more aggressive cancer in some tumor types.2-4

IHC FISH RNA Fusions by NGS
  • Inexpensive methodology
  • Rapid turnaround time
  • Location of the target within the cell is visible7,8
  • High sensitivity and specificity8
  • Detection of novel fusion partners (depending on method)10
  • Ability to interrogate multiple genomic alterations simultaneously10
  • Growing relevance as NGS can accurately detect many genomic alterations in therapeutically relevant cancer genes in a single assay5,6
  • Detects both fusion and wild type TRK expression5
  • Not all neoplasms are appropriate for IHC screening
  • Pan-TRK IHC lacks the specificity required for a definitive, stand-alone assay6
  • Requires fluorescence microscopy8
  • Target sequence must be known (break-apart FISH may detect NTRK gene fusions with unknown partners, but both in-frame and out-of-frame fusions will be detected)10
  • Some intra-chromosomal fusions may not be detected
  • Turnaround time is generally longer than other methodologies

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References:

  1. Hsiao, Susan J., et al. (2019) Jour Molec Diag.
  2. Stransky N, et al. Nat Commun. 2014;5:846.
  3. Park DY, et al. Oncotarget. 2015;7(7):8399-8412.
  4. Vaishnavi A, et al. Cancer Discov. 2015;5:25-34.
  5. Bourgeois JM et al. Am J Surg Pathol. 2000;24:937-946
  6. Murphy D. et al Appl lmmunohistochem Mol Morphol 2017:25:513-523.
  7. Kerr KM, Lopez-Rios F. Ann Oncol. 2016;27:iii16-iiii24.
  8. Cui C. et al. Front Cell Dev Biol. 2016;4:89
  9. Chae YK, et al Oncotarget. 2017;8:100863-100898.
  10. Church AJ, et al. Mod Pathol. 2018;31:463-473.