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Home > A. Molecular pathology > Fusion genes > ETV6-NTRK3


Thursday 19 June 2003


Definition: The fusion gene ETV6-NTRK3 is created by the t(12;15)(p13;q25). It encodes a fusion protein with the sterile alpha motif (SAM) oligomerization domain of ETV6 in N-term to the C- term protein tyrosine kinase (PTK) domain of NTRK3 .

The fusion gene ETV6/NTRK3 functions as a constitutively active tyrosine kinase.

ETV6-NTRK3 is capable of homodimerization, or heterodimerization with ETV6, and subsequent PTK activation, leading to constitutive elevation of cyclin D1, and increased cell cycle progression.

ETV6-NTRK3 also leads to constitutive activation of two of the major effector pathways of NTRK3: the Ras-MAPK mitogenic pathway and the phosphatidyl inositol-3-kinase (PI3K) pathway leading to activation of the AKT cell survival factor (Lannon and Sorensen, 2005).


- ETV6-NTRK3 fusion gene by translocation t(12;15)(p13;q25) in :


- chimeric protein tyrosine kinase ETV6-NTRK3 requires both Ras-Erk1/2 and PI3-kinase-Akt signaling for fibroblast transformation (11751416)

- ETV6-NTRK3 transformation requires insulin-like growth factor 1 receptor signaling and is associated with constitutive IRS-1 tyrosine phosphorylation (12173038)

Paywall References

- Clinical and Morphologic Features of ETV6-NTRK3 Translocated Papillary Thyroid Carcinoma in an Adult Population Without Radiation Exposure. Seethala RR, Chiosea SI, Liu CZ, Nikiforova M, Nikiforov YE. Am J Surg Pathol. 2017 Jan 25. doi : 10.1097/PAS.0000000000000814
PMID: 28125451

- Mammary Analogue Secretory Carcinoma of Salivary Glands, Containing the ETV6-NTRK3 Fusion Gene: A Hitherto Undescribed Salivary Gland Tumor Entity. Skálová A, Vanecek T, Sima R, Laco J, Weinreb I, Perez-Ordonez B, Starek I, Geierova M, Simpson RH, Passador-Santos F, Ryska A, Leivo I, Kinkor Z, Michal M. Am J Surg Pathol. 2010 Apr 20. PMID: 20410810

- Bourgeois JM, Knezevich SR, Mathers JA, Sorensen PH. Molecular detection of the ETV6-NTRK3 gene fusion differentiates congenital fibrosarcoma from other childhood spindle cell tumors. Am J Surg Pathol. 2000 Jul;24(7):937-46. PMID: 10895816

- A unique translocation of the TEL gene in a case of acute myelogenous leukemia with inv(12)(p13q15). Setoyama M, Tojo A, Nagamura F, Asano S, Ishimae M, Eguchi M, Kamada N. Blood. 1998 ; 92 (4) : 1454-1455. PMID 9694736

- Fusion of ETV6 to neurotrophin-3 receptor TRKC in acute myeloid leukemia with t(12;15)(p13;q25). Eguchi M, Eguchi-Ishimae M, Tojo A, Morishita K, Suzuki K, Sato Y, Kudoh S, Tanaka K, Setoyama M, Nagamura F, Asano S, Kamada N. Blood. 1999 ; 93 (4) : 1355-1363. PMID 9949179

- ETV6-NTRK3: a chimeric protein tyrosine kinase with transformation activity in multiple cell lineages. Lannon CL, Sorensen PH. Seminars in cancer biology. 2005 ; 15 (3) : 215-223. PMID 15826836