title: ETV6-NTRK3: a chimeric protein tyrosine kinase with transformation activity in multiple cell lineages.
abstract: The ETV6-NTRK3 (TEL-TRKC) gene fusion was discovered by breakpoint analysis of the t(12;15)(p13;q25) translocation associated with congenital fibrosarcoma, a pediatric soft tissue malignancy. ETV6-NTRK3 (EN) encodes the sterile alpha motif oligomerization domain of the ETV6 (TEL) transcription factor linked to the protein tyrosine kinase domain of the neurotrophin-3 receptor NTRK3 (TRKC). The EN chimeric oncoprotein links to multiple signaling cascades including Ras-MAP kinase and PI3K-AKT through the IRS-1 adapter protein. Recent evidence indicates that a functional insulin-like growth factor 1 receptor axis and higher order polymer formation are essential for EN oncogenesis. EN has been detected in other malignancies, including secretory breast carcinoma. This chimeric oncoprotein is therefore unique in being expressed in tumors derived from multiple cell lineages.
authors.affiliation: Johal Program in Pediatric Oncology Basic and Translational Research, Departments of Pathology and Pediatrics, BC Research Institute for Children's and Women's Health, and the University of British Columbia, Vancouver, BC, Canada V5Z4H4.
authors.forename: Chris L
authors.initials: CL
authors.lastname: Lannon
authors.forename: Poul H B
authors.initials: PH
authors.lastname: Sorensen
mesh_terms: D000818:Animals; D019070:Cell Lineage; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D020812:Receptor, trkC; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D015514:Oncogene Proteins, Fusion; D011505:Protein-Tyrosine Kinases; C484319:ETV6-NTRK3 fusion protein, human; D020812:Receptor, trkC; D000097764:ETS Translocation Variant 6 Protein