NTRK1 was originally detected as an oncogene (named TRK) in a human colon cancer, following transfection of tumoural high molecular weight DNA in NIH 3T3 cells and focus formation (Martin-Zanca et al, 1986). This activated version of the proto-oncogene was generated by a somatic intrachromosomal rearrangement fusing the tyrosine kinase (TK) domain of NTRK1 with 5￠ sequences of the non-muscular tropomyosin gene (TPM3). NTRK1 proto-oncogene rearrangements have been described also in human papillary thyroid carcinomas (PTC). In these cancers, the NTRK1 oncogenic rearrangements are the consequence of the fusion of the TK domain of NTRK1 with at least three different genes: the TPM3 gene as found in the original TRK oncogene; the TPR (translocated promoter region) gene, also located on chromosome 1q and first identified as part of the MET oncogene (TPRMET), giving rise at two different oncogenes: TRK-T1 and TRK-T2; and the TFG (TRK-fused gene) gene which function is unknown and located on chromosome 3, originating the TRK-T3 oncogene. All these oncogenic forms of NTRK1 encode cytoplasmic chimaeric proteins which are constitutively phosphorylated on tyrosine.
Bounacer A, Schlumberger M, Wicker R, et al. Search for NTRK1 proto-oncogene rearrangements in human thyroid tumours originated after therapeutic radiation[J]. British journal of cancer, 2000, 82(2): 308.