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Factors to Consider When Developing Laboratory Algorithms for NTRK Fusion Testing

By: Amy MacDonald, MS
Posted: Thursday, March 9, 2023

NTRK fusions have been identified as important targets in the treatment of several cancers. Although NTRK fusions are rarely found in the most common tumor types (eg, lung, breast, colorectal, prostate), such fusions appear to be more prevalent in rarer tumor types (eg, sarcomas, pediatric mesenchymal tumors, and thyroid cancer), necessitating the development of effective and cost-sensitive methods to determine which patients would benefit most from NTRK-targeted therapies. Sophia Louise Yohe, MD, of the University of Minnesota, Minneapolis, and colleagues compared different NTRK testing methods to help clinicians make informed choices for their laboratories. The team published their report in the Archives of Pathology and Laboratory Medicine.

The researchers performed a comprehensive PubMed literature search (January 2015–May 2020) and found 207 NTRK-related articles. Data—which included but were not limited to tumor type, type of NTRK genetic alteration, testing method, and drug therapy chosen—were extracted from the articles and evaluated.

Four main conclusions were drawn by the investigators. First, the next-generation sequencing panel testing is a cost-effective and reliable way to detect NTRK fusions in certain tumor types. However, the design of the panel (and the decision to use DNA or RNA) matters. Second, pan-TRK immunohistochemistry may be considered as a rapid and less-expensive screening option in situations where the sample will not undergo routine next-generation sequencing testing. Third, fluorescence in situ hybridization may be appropriate for low tumor–content specimens that are unsuitable for next-generation sequencing testing. Fourth, quantitative reverse-transcription polymerase chain reaction should be selected when monitoring low-level disease of a specific, previously identified target.

The authors determined that a thorough understanding of these considerations would benefit laboratories that seek to develop their own NTRK testing protocols.

Disclosure: Eric E. Walk, MD, is an employee of PathAI and a Roche shareholder. All other study authors reported no conflicts of interest.

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