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).
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.