NTRK Fusions

There are 3 NTRK genes (1, 2, and 3) that contain the information for making three similar proteins: TRK-A, TRK-B, and TRK-C. The normal TRK proteins are receptors mostly found on the surface of cells of the nervous system. Their role is to receive signals from neighboring neurons to instruct cells to grow and divide.¹ It is rare but the NTRK genes can fuse with other non-related genes which then produce new NTRK fusion proteins that promote uncontrolled cell growth and division in cancer cells.

NTRK fusions are very rare in metastatic colorectal cancer and therefore routine testing is not recommended. The NTRK fusion is different from a mutation. The fusion will be reported if you have comprehensive biomarker testing by Next Generation Sequencing (NGS).

Individual NTRK fusion testing should be limited to those that are wildtype (no mutations) in KRAS, BRAF, NRAS and MSI-H. This testing can be done using different methods.

NTRK fusion proteins are seen more commonly in microsatellite instability (MSI-H) tumors. ⁴

There are several ways to test for NTRK fusions. All testing should be done in CLIA-certified laboratories. It is recommended that all positive results be confirmed using one of the other available methods.