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Advantages

The advantages of RNA-based NGS are those common to all NGS techniques as well as those specific to RNA-based NGS, as shown in the following table.

Table 23: Advantages of RNA-based NGS for Testing for NTRK Gene Fusions

Advantages

  • Screens multiple genes for fusions.
  • Confirms the presence of transcription.
  • Allows large expansion (multiplexing) of the number of targets and throughput of diagnostic testing [1, 2].
  • Meets or exceeds the sensitivity of other methods (i.e. FISH) for detecting gene fusions [2].
  • Avoids technical complications associated with the effect of large intronic spaces in detecting NTRK gene fusions [3, 4].
  • Allows detection of novel partners [2, 5, 6].
  • Requires no prior knowledge of fusion partners or of intron/exon breakpoints [3].

 References

  1. 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.
  2. Beadling C, Wald AI, Warrick A et al. A Multiplexed Amplicon Approach for Detecting Gene Fusions by Next-Generation Sequencing. J Mol Diagn 2016; 18: 165-175.
  3. Kheder ES, Hong DS. Emerging Targeted Therapy for Tumors with NTRK Fusion Proteins. Clin Cancer Res 2018; 24: 5807-5814.
  4. Choi Y, Won YJ, Lee S et al. Cytoplasmic TrkA Expression as a Screen for Detecting NTRK1 Fusions in Colorectal Cancer. Transl Oncol 2018; 11: 764-770.
  5. Chen Y, Chi P. Basket trial of TRK inhibitors demonstrates efficacy in TRK fusion-positive cancers. J Hematol Oncol 2018; 11: 78.
  6. Church AJ, Calicchio ML, Nardi V et al. Recurrent EML4-NTRK3 fusions in infantile fibrosarcoma and congenital mesoblastic nephroma suggest a revised testing strategy. Mod Pathol 2018; 31: 463-473.

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