Detection of NTRK fusions: Merits and limitations of current diagnostic platforms

Abstract

Oncogenic fusions involving NTRK1, NTRK2, and NTRK3 with various partners are diagnostic of infantile fibrosarcoma and secretory carcinoma yet also occur in lower frequencies across many types of malignancies. Recently, targeted small molecular inhibitor therapy has been shown to induce a durable response in a high percentage of patients with NTRK fusion-positive cancers, which has made the detection of NTRK fusions critical. Several techniques for NTRK fusion diagnosis exist, including pan-Trk IHC, FISH, reverse transcription PCR, DNA-based next-generation sequencing (NGS), and RNA-based NGS. Each of these assays has unique features, advantages, and limitations, and familiarity with these assays is critical to appropriately screen forNTRKfusions. Here, we review the details of each existing methodology.