Applications in NTRK Gene Fusion Testing

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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]. The DNA- or protein-based methods are not as commonly used as RNA-based NGS sequencing [5]. 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].

 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.
  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. Zheng Z, Liebers M, Zhelyazkova B et al. Anchored multiplex PCR for targeted next-generation sequencing. Nat Med 2014; 20: 1479-1484.
  7. Kheder ES, Hong DS. Emerging Targeted Therapy for Tumors with NTRK Fusion Proteins. Clin Cancer Res 2018; 24: 5807-5814.
  8. 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.
  9. Chen Y, Chi P. Basket trial of TRK inhibitors demonstrates efficacy in TRK fusion-positive cancers. J Hematol Oncol 2018; 11: 78.
Last update: 24 June 2019