Mutated genes in cancer (64) – NTRK3

Mutated genes in cancer (64) – NTRK3

NTRK3

In databases:

● Entrez (http://www.ncbi.nlm.nih.gov/sites/gquery): 4916 or NTRK3

● Ensembl (http://www.ensembl.org/index.html): ENSG00000140538

● UniProt (http://www.uniprot.org/): Q16288

● OMIM (http://www.ncbi.nlm.nih.gov/omim): 191316

● GeneCards (http://www.genecards.org/): NTRK3

● HGNC (http://www.genenames.org/): 8033 or NTRK3

● Enzyme Number (IUBMB): EC 2.7.10.-, EC 2.7.10.1

Gene locus:

15q25

Protein name:

Neurotrophic tyrosine kinase, receptor, type 3

Protein Size:

839 amino acids; about 94 kDa

Function:

NTRK3 encodes a tyrosine-protein kinase receptor for neurotrophin-3 (NT-3). Upon neurotrophin binding, NTRK3 phosphorylates itself and members of the MAPK pathway. Signalling through this kinase leads to neuronal proliferation and differentiation.

Cancer-related alterations:

Somatic NTRK3 mutations (“substitution missense”) have been found in a small (<3%) percentage of lung, skin, stomach, breast and tumors. There are no mutation hot spots.

NTRK3 is involved in fusions with ETV6 in congenital fibrosarcoma (CFS) and congenital mesoblastic nephroma-cellular variant (cellular CMN), which are pediatric tumors of mesoblastic origin. ETV6-NTRK3 gene fusions are the result of a t(12;15)(p13;q25) translocation. This translocation and the resulting ETV6-NTRK3 fusion are also found in secretory breast carcinoma, which is an epithelium derived breast cancer.

References (open access):

Identification and preclinical characterization of AZ-23, a novel, selective, and orally bioavailable inhibitor of the Trk kinase pathway. Thress K, Macintyre T, Wang H, Whitston D, Liu ZY, Hoffmann E, Wang T, Brown JL, Webster K, Omer C, Zage PE, Zeng L, Zweidler-McKay PA. Mol Cancer Ther. 2009 Jul;8(7):1818-27.

http://mct.aacrjournals.org/content/8/7/1818.full.pdf+html

Secretory breast carcinomas with ETV6-NTRK3 fusion gene belong to the basal-like carcinoma spectrum. Laé M, Fréneaux P, Sastre-Garau X, Chouchane O, Sigal-Zafrani B, Vincent-Salomon A. Mod Pathol. 2009 Feb;22(2):291-8.

http://www.nature.com/modpathol/journal/v22/n2/pdf/modpathol2008184a.pdf

ETV6-NTRK3 fusion oncogene initiates breast cancer from committed mammary progenitors via activation of AP1 complex. Li Z, Tognon CE, Godinho FJ, Yasaitis L, Hock H, Herschkowitz JI, Lannon CL, Cho E, Kim SJ, Bronson RT, Perou CM, Sorensen PH, Orkin SH. Cancer Cell. 2007 Dec;12(6):542-58.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2175032/pdf/nihms36102.pdf