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Alexander Drilon, MD

Gregory J. Riely, MD, PhD


RNA-Based Assay Identifies NTRK Gene Fusions in a Pan-Cancer Setting

By: Julia Fiederlein
Posted: Friday, August 19, 2022

As a result of the approval of TRK inhibitors in the treatment of NTRK gene fusion–positive tumors by the U.S. Food and Drug Administration and the European Medicines Agency, a variety of testing algorithms have been proposed. A study conducted by Laure Sorber, PhD, of the University of Antwerp, Wilrijk, Belgium, and colleagues demonstrated the potential of an RNA-based assay to identify NTRK gene fusions in a pan-cancer setting. Their findings were published in The Journal of Molecular Diagnostics.

“Major advantages of this assay include the fact that it is fully automated with a short turnaround time, as well as its robustness to process older formalin-fixed, paraffin-embedded samples,” the investigators commented. “However, it might be necessary to interpret results obtained by the…assay per cancer type.”

The performance of this experimental testing modality was evaluated in a set of clinically relevant cancer types, including glioblastoma, non–small cell lung cancer (NSCLC), microsatellite instability–positive colorectal cancer, and thyroid carcinoma. The baseline RNA expression profiles seemed to significantly differ between the cancer types; this appeared to correlate with the findings of The Cancer Genome Atlas and consensus data sets, as well as the results of pan-TRK immunohistochemistry. Compared with an RNA-based next-generation sequencing technique, the experimental testing modality demonstrated an overall percentage agreement of 92.7%, a positive percentage agreement of 81.8%, and a negative percentage agreement of 93.8%; based on the results of pan-TRK immunohistochemistry, these values were 82.1%, 45.5%, and 85.7%, respectively.

The efficiency of detecting NTRK gene fusions was compared among four testing modalities; the investigators reported a high concordance within the polymerase chain reaction–based methods. When using the experimental testing modality, a significant amount of RNA degradation and/or loss was observed in snap-frozen tissue samples; according to the investigators, this may be countered by increasing the amount of sample input.

Disclosure: For full disclosures of the study authors, visit

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