ETV6-NTRK3 gene fusion is the translocation of genetic material between the ETV6 gene located in the short arm (designated p) of chromosome 12 at position p13.2 (ie 12p13.2) and gene NTRK3 located at the long arm (designated q) of chromosome 15 at position q25.3 (ie 15q25.3) to create fusion (12; 15) (p13; q25) gene, ETV6-NTRK3 . This new gene consists of the 5 ' ETV6 ends that blend with the 3' end of NTRK3 . ETV6-NTRK3 therefore the code for the chimeric oncoprotein comprising the helix-loop-helix (HLH) dimerization domain of ETV6 protein integrates with the tyrosine kinase domain (ie PTK) of the NTRK3 protein. The ETV6 code gene for transcription factor protein ETV6, which suppresses expression, and thus regulates, the genes that rats are required for normal hematopoiesis as well as the development and maintenance of vascular tissue. NTRK3 code for receptors Tropomiosin kinase C a surface protein of NT-3 growth factor receptor cells that, when attached to its growth factor ligand, neurotropin-3, becomes an active tyrosine kinase that phosphorylates the tyrosine residue, and thus stimulates, signaling proteins that promote growth, survival, and proliferation of stem cells. The tyrosine Kinase of the dysfunctional ETV6-NTRK3 fusion protein is in that it is continuously active in phosphorylating tyrosine residues, and thus continues to stimulate, proteins that promote the growth, survival, and proliferation of their stem cells. Therefore, these cells take on a malignant character and are on track to become cancerous. Indeed, the fusion gene ETV6-NTRK3 appears to be a critical driver of some cancers. It was initially identified in congenital fibrosaroma and later found in secretory breast cancer (also called adolescent breast cancer), mammary secretory carcinoma of the salivary glands (also called MASC or MASC SG ), congenital fibrosarcomas, mesoblastic congenital nephroma , a rare case of acute myelogenous leukemia, ALK-negative Myofibroblastic tumor inflammation, and induced radiation papyric thyroid carcinoma.
Video ETV6-NTRK3 gene fusion
NTRK3 inhibitor in clinical development
Since the cancer associated with expression of the ETV6-NTRK3 fusion protein is known or suspected as a direct consequence of an overactive transient ETV6-NTRK3 tyrosine kinase, it has been proposed that a tyrosine kinase inhibitor with specificity for NTRK3 may be of therapeutic use in this regard. cancer. Entrectinib is a pan-NTRK as well as a tyrosine kinase inhibitor of ALK and ROS1 has been found useful in treating single patients with the mammary analogous carcinoma gene carcinoma gene associated with the ETV6-NRTK3 gene and has provided support to the clinical development of tyrosine kinase inhibitors NTRK3 directed to treat ETV6-NTRK3-associated fungus protein. Three clinical trials are in the recruitment phase to determine the efficacy of treating various solid tumors associated with mutated overactive mutinous tyrosine kinase proteins, including ETV6-TRK3 protein, with larotrectinib, NTRK1 non-selective inhibitors, NTRK2, and NTRK3 tyrosine kinases.
Maps ETV6-NTRK3 gene fusion
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