Genes

NTRK1 (TRKA)

NTRK1 (neurotrophic tyrosine kinase, receptor, type 1) is a receptor tyrosine kinase that is part of the TRK (tropomyosin-related kinases) superfamily of receptor tyrosine kinases (Nakagawara 2001; Sossin 2006). The NTRK1 gene is located on chromosome 1q21-22 and encodes high affinity nerve growth factor receptor (TRKA). NTRK1 acts in control of cell growth and differentiation via the MAPK, PI3K and PLC-γ pathways when activated by the NGF ligand (Alberti et al. 2003).

NTRK1 fusions were initially reported in one case of colorectal cancer (Martin-Zanca et al. 1986). NTRK1 rearrangements have been reported in 12% of papillary thyroid cancer (Greco et al. 2010), 3.3% of lung cancer (Vaishnavi et al. 2013), and approximately 1% of glioblastoma multiforme cases (Greco et al. 2010; Kim et al. 2014). Recently, one case of a RABGAP1L-NTRK1 fusion has been reported in cholangiocarcinoma (Ross et al. 2014). In colorectal and thyroid cancer, the fusion partners include TPM3, TFG and TPR (Martin-Zanca et al. 1986). In lung cancer, fusion partners identified include MPRIP and CD74 (Vaishnavi et al. 2013).

NTRK1 gene fusions include the entire kinase domain of TRKA (the protein product from the NTRK1 gene). NTRK1 gene fusions tested trigger constitutive TRKA kinase activity (Vaishnavi et al. 2013).

ntrk1-pathway.png

Figure 1.
Schematic representation of NTRK1 (TRKA) fusions. "X" represents the various fusion partners that have been described. Dimerization of the NTRK1 fusion mediated by the fusion partner ("X"), results in constitutive activation of the NTRK1 tyrosine kinase. NTRK1 signaling results in pro-growth and anti-apoptosis effects.

Related Pathways

​​

Contributors: Christine M. Lovly, M.D., Ph.D., Robert C. Doebele, M.D., Ph.D.

Suggested Citation: Lovly, C.M., Doebele, R.C. 2015. NTRK1 (TRKA). My Cancer Genome https://www.padiracinnovation.org/content/gene/ntrk1/ (Updated December 2015)

Modified: December 7, 2015

Disclaimer: The information presented at padiracinnovation.org is compiled from sources believed to be reliable. Extensive efforts have been made to make this information as accurate and as up-to-date as possible. However, the accuracy and completeness of this information cannot be guaranteed. Despite our best efforts, this information may contain typographical errors and omissions. The contents are to be used only as a guide, and health care providers should employ sound clinical judgment in interpreting this information for individual patient care.