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

• Published in: Cancer research (Chicago, Ill.) Vol. 79; no. 13; pp. 3163 - 3168
• Main Authors: Solomon, James P, Hechtman, Jaclyn F
• Format: Journal Article
• Language: English
• Published: United States 01-07-2019
• Subjects: Biomarkers, Tumor - genetics; Gene Rearrangement; Humans; Neoplasms - diagnosis; Neoplasms - genetics; Oncogene Proteins, Fusion - genetics; Receptor, trkA - genetics; Receptors, Nerve Growth Factor - genetics
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.CAN-19-0372

Oncogenic fusions involving
, and
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
fusion-positive cancers, which has made the detection of
fusions critical. Several techniques for
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 for
fusions. Here, we review the details of each existing methodology.