TRK Gene Fusions

TRK gene is essential for cellular growth and division, but fusion of this gene can lead to growth of cancer cells. Precision medicine is a targeted treatment, based on inidividual's unique cancer and aimed at stopping disease in its tracks. TRK gene fusions are also sometimes called as NTRK gene fusions. TRK is classified as “oncogene,” meaning that damage to these inherited DNA sequences can occur in healthy cells and cause them to form tumors. Cancer cells then come to depend on the altered genes and their new protein products for survival.

  • NTRK genes code for TRK proteins

    • Neurotrophic tyrosine kinase (NTRK) is the name of the family of three genes encoding tropmomyosin receptor kinases (TRK) A, B, and C.

  • Fusion genes and their proteins

    • 5’Partner-3’NTRK fusion genes are translated into fusion proteins with an N-terminal from the fusion partner and the kinase domain of TRK at the C-terminal.

  • Examples of TRK fusions:

    • TPM3-NTRK1  is a fusion between the cytoskeletal protein tropomyosin and TRKA
    • BCAN-NTRK1  is a fusion between extracellular matrix protein brevican and TrkA.
    • LMNA-NTRK1 is a fusion between the nuclear matrix protein laminin A/C and the kinase domain of TRKA.
    • NFASC-NTRK1 is a fusion between neurofascin and TRKA
    • SQSTM1-TRK1 is a fusion between the scaffold protein  p62 (a.k.a sequestosome 1) and TRKA
    • ETV6-NTRK3 is a fusion between the multi-functional transcription factor TEL and the kinase domain of TRKC.

  • What are TRK (NTRK) Genetic Abnormalities?

    • When TRK gets fused (connected) to other genes then it leads the cell to a path of abnormal behavior causing many types of cancer in humans.