Detecting TRK Fusions

TRK

TRK pathway signaling

Watch this video to learn how TRK fusions activate signaling that may lead to uncontrolled growth in multiple tumors.

TRK fusions can be detected with various testing methods1,2

Next-generation sequencing (NGS)1-4

  • Multigene parallel sequencing assay1
  • Provides information about multiple biomarkers, including rare and common mutations, and can typically use less tissue1,3
  • Can detect fusions in all 3 NTRK genes, as well as other genetic alterations2
  • Can detect TRK fusion partner and position2
  • Turnaround time for results may be longer than with IHC or FISH4

Immunohistochemistry (IHC)1,3,5

  • Uses specific antibodies to detect overexpression of the TRK fusion protein1
  • Can be used to screen patients for TRK fusions, if included in panels1
  • Requires dedicated tissue and limits multiplexing3,5
  • Only detects the TRK component of the fusion protein; molecular confirmation is necessary1

Fluorescence in situ hybridization (FISH)1,4,6

  • Uses “break-apart” probes to show TRK gene rearrangement1
  • Requires dedicated tissue6
  • Delivers rapid results4
  • Cannot distinguish fusion variants4
  • May be labor intensive, possibly more expensive for multiple assays1

TRK=tropomyosin receptor kinase; NTRK=neurotrophic tyrosine receptor kinase.

References

  1. Murphy DA, Ely HA, Shoemaker R, et al. Appl Immunohistochem Mol Morphol. 2017;25(7):513-523. PMID: 27028240
  2. Vaishnavi A, Le AT, Doebele RC. Cancer Discov. 2015;5(1):25-34. PMID: 25527197
  3. Su D, Zhang D, Chen K, et al. J Exp Clin Cancer Res. 2017;36(1):121. PMID: 28882180
  4. Hechtman JF, Benayed R, Hyman DM, et al. Am J Surg Pathol. 2017;41(11):1547-1551. PMID: 28719467
  5. Stack EC, Wang C, Roman KA, Hoyt CC. Methods. 2014;70(1):46-58. PMID: 25242720
  6. Knezevich SR, McFadden DE, Tao W, Lim JF, Sorensen PH. Nat Genet. 1998;18(2):184-187. PMID: 9462753