Neurotrophic tropomyosin or tyrosine receptor kinase (NTRK) genes

The neurotrophic tropomyosin or tyrosine receptor kinase (NTRK) genes (1-3) are proto-oncogenes that when activated are encountered in a wide array of tumours. The recent advent of very specific and selective inhibitors of their gene fusions makes the NRTK gene fusions actionable. NRTK gene fusions are very characteristic of specific tumours: salivary mammary analogue secretory carcinoma, breast secretory carcinoma, infantile fibrosarcoma and congenital mesoblastic nephroma. Over 90% of these tumours bear NTRK gene fusions. While next-generation sequencing is the current platform of choice for the detection of NTRK fusions, immunohistochemistry also shows great promise. Immunohistochemical localisation of the fusion protein to the nucleus, cytoplasm, nuclear membrane and cell membrane is indicative of specific gene fusions involving the NTRK genes.