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Overview

Translocations can occur anywhere in the genome, including coding regions, introns, and other non-coding sequences. As translocations may not be expressed and have limited biological relevance, DNA might not be the ideal substrate to identify oncogenic fusions [1]. As shown in the figure below, RNA-based NGS avoids the technical complications associated with the effect of large intronic spaces in detecting NTRK gene fusions, as the intron regions are not present in the mRNA transcript [2-4].

Figure 12: RNA-based NGS Avoids the Technical Complications Associated with Large Intronic Spaces

Figure 12: RNA-based NGS Avoids the Technical Complications Associated with Large Intronic Spaces

Although there are many platforms available, the basic steps in performing RNA-based NGS are summarised in the following figure.

Click here for an overview of DNA- and RNA-based NGS.

 References

  1. Zheng Z, Liebers M, Zhelyazkova B et al. Anchored multiplex PCR for targeted next-generation sequencing. Nat Med 2014; 20: 1479-1484.
  2. Kheder ES, Hong DS. Emerging Targeted Therapy for Tumors with NTRK Fusion Proteins. Clin Cancer Res 2018; 24: 5807-5814.
  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.

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