Gene expression of TrkC (NTRK3) in human soft tissue tumours

TrkC is a member of the Trk family of tyrosine kinase receptors and plays an important role in the development and maintenance of neural tissues. Although a variety of non-neuronal tissues have also been shown to express TrkC, the status of TrkC in soft tissue tumours has been poorly investigated, except for a small fraction of tumours including congenital/infantile fibrosarcoma characterized by an ETV6-NTRK3 (also known as Tel-TrkC) fusion gene. To broaden knowledge about the TrkC status in human neoplasms, the expression of TrkC transcripts was assessed in 51 soft tissue tumours of variable lines of differentiation by reverse transcription-polymerase chain reaction (RT-PCR), using primer sets flanking their extracellular domain, the tyrosine kinase domain, and the intracellular domain of a truncated variant (Trunc 1) described previously. In 44 of the 51 tumours, TrkC transcripts, including alternatively spliced isoforms, were detected. The truncated transcripts (Trunc 1) were co-expressed in 40 of the 44 tumours and were expressed in one tumour without native TrkC gene expression. In two of the remaining six tumours, part of the sequence coding the tyrosine kinase domain of TrkC appeared to be truncated. Using a 3' rapid amplification of cDNA ends (3'RACE) method, another truncated isoform (Trunc 2) was isolated from one of the tumours, in which the TrkC transcript was terminated with a novel 160-base pair sequence. This truncated isoform was identified in nine of the 51 tumours examined by RT-PCR using primers for Trunc 2. There was no clear correlation between the types of TrkC isoforms detected and histological types or grades of the tumours. These results suggest that human soft tissue tumours widely express TrkC, irrespective of their cellular lineage, morphology, and biological behaviour. Dysregulated TrkC expression may enhance overgrowth or transformation of various mesenchymal cells.