Rearrangements of NTRK1 gene in papillary thyroid carcinoma

TRK oncogenes are observed in a consistent fraction of papillary thyroid carcinoma (PTC); they arise from the fusion of the 3′ terminal sequences of the NTRK1/NGF receptor gene with 5′ terminal sequences of various activating genes, such as TPM3, TPR and TFG. TRK oncoproteins display constitutive tyrosine-kinase activity, leading to in vitro and in vivo transformation. In this review studies performed during the last 20 years will be summarized. The following topics will be illustrated: (a) frequency of TRK oncogenes and correlation with radiation and tumor histopathological features; (b) molecular mechanisms underlying NTRK1 oncogenic rearrangements; (c) molecular and biochemical characterization of TRK oncoproteins, and their mechanism of action; (d) role of activating sequences in the activation of TRK oncoproteins.