Detection of NTRK Fusions: Merits and Limitations of Current Diagnostic Platforms

Area of Science:

• Molecular Oncology
• Genetics
• Cancer Diagnostics

Background:

• Oncogenic NTRK gene fusions (NTRK1, NTRK2, NTRK3) are key drivers in specific cancers like infantile fibrosarcoma and secretory carcinoma.
• These fusions are increasingly found in various malignancies, necessitating accurate detection for effective treatment.
• Targeted therapies show high response rates in NTRK fusion-positive cancers, underscoring the importance of diagnostic assays.

Purpose of the Study:

• To review and compare existing methodologies for detecting NTRK gene fusions.
• To provide insights into the advantages and limitations of each diagnostic technique.
• To emphasize the critical role of familiarity with these assays for appropriate screening.

Main Methods:

• Review of established diagnostic techniques including pan-Trk immunohistochemistry (IHC).
• Analysis of fluorescence in situ hybridization (FISH) and reverse transcription polymerase chain reaction (RT-PCR).
• Evaluation of next-generation sequencing (NGS) approaches, both DNA-based and RNA-based.

Main Results:

• Each reviewed method (IHC, FISH, RT-PCR, DNA-NGS, RNA-NGS) possesses distinct characteristics.
• Understanding the specific features, benefits, and drawbacks of each assay is essential for clinical application.
• No single method is universally superior; assay selection depends on clinical context and diagnostic goals.

Conclusions:

• Accurate identification of NTRK fusions is paramount for guiding targeted therapy in cancer patients.
• A comprehensive understanding of available diagnostic tools is necessary for effective NTRK fusion screening.
• Continued evaluation and appropriate application of these methodologies will improve patient outcomes.