Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Previous Page Next Page

To date, clinical detection of NTRK gene fusions has predominantly utilised DNA- or RNA-based NGS [1-3].

Selection of NGS platforms is critical as not all assays are optimised to detect these fusions [4]. DNA- or protein-based methods are not as commonly used as RNA-based NGS sequencing [5]. RNA-based sequencing appears to be the optimal way to approach NTRK fusions because the splicing out of introns simplifies the technical requirements of adequate coverage and because detection of RNA-level fusions provides direct evidence of functional transcription. However, even though it provides many advantages, RNA-based testing is not perfect [6].

AMP is a more recent platform that allows for rapid enrichment for targeted RNA and DNA NGS [6]. AMP can detect gene fusions, point mutations, insertions, deletions and copy number changes from low amounts of RNA and DNA in formalin-fixed paraffin-embedded samples [6].

Notable limitations that restrict widespread use of NGS platforms are the inability of some panels to detect all types of NTRK gene fusions [4, 7], as well as the cost, complexity and labour intensity of testing [8, 9]. However, as technology advances suitable platforms are becoming increasingly available and established for use in detection of NTRK gene fusions [10, 11].

 References

  1. Cocco E, Scaltriti M, Drilon A. NTRK fusion-positive cancers and TRK inhibitor therapy. Nat Rev Clin Oncol 2018; 15: 731-747.
  2. Albert CM, Davis JL, Federman N et al. TRK Fusion Cancers in Children: A Clinical Review and Recommendations for Screening. J Clin Oncol 2019; 37: 513-524.
  3. Penault-Llorca F, Rudzinski ER, Sepulveda AR. Testing algorithm for identification of patients with TRK fusion cancer. J Clin Pathol 2019.72(7): 460-467.
  4. Cocco E, Scaltriti M, Drilon A. NTRK fusion-positive cancers and TRK inhibitor therapy. Nat Rev Clin Oncol 2018; 15: 731-747.
  5. Kumar-Sinha C, Kalyana-Sundaram S, Chinnaiyan AM. Landscape of gene fusions in epithelial cancers: seq and ye shall find. Genome Med 2015; 7: 129.
  6. Solomon JP, Linkov I, Rosado A et al.NTRK fusion detection across multiple assays and 33,997 cases: diagnostic implications and pitfalls. Mod Pathol. 2020; 33(1):38-46.
  7. Zheng Z, Liebers M, Zhelyazkova B et al. Anchored multiplex PCR for targeted next-generation sequencing. Nat Med 2014; 20: 1479-1484.
  8. Kheder ES, Hong DS. Emerging Targeted Therapy for Tumors with NTRK Fusion Proteins. Clin Cancer Res 2018; 24: 5807-5814.
  9. Zehir A, Benayed R, Shah RH et al. Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients. Nat Med 2017; 23: 703-713.
  10. Chen Y, Chi P. Basket trial of TRK inhibitors demonstrates efficacy in TRK fusion-positive cancers. J Hematol Oncol 2018; 11: 78.
  11. Pfarr N, Kirchner M, Lehmann U, et al. Testing NTRK testing: Wet-lab and in silico comparison of RNA-based targeted sequencing assays. Genes Chromosomes Cancer. 2020 Mar;59(3):178-188.

  12. Kirchner M, Glade J, Lehmann U, et al. NTRK testing: First results of the QuiP-EQA scheme and a comprehensive map of NTRK fusion variants and their diagnostic coverage by targeted RNA-based NGS assays. Genes Chromosomes Cancer. 2020; 59(8):445-453.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.