Oncogenic and drug sensitive NTRK1 rearrangements in lung cancer

We identified novel gene fusions in patients with lung cancer harboring the kinase domain of the NTRK1 gene that encodes the TRKA receptor. Both the MPRIP-NTRK1 and CD74-NTRK1 fusions lead to constitutive TRKA kinase activity and are oncogenic. Treatment of cells expressing NTRK1 fusions with inhibi...

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Detalles Bibliográficos
Autores principales: Vaishnavi, A., Capelletti, M., Le, A.T., Kako, S., Butaney, M., Ercan, D., Mahale, S., Davies, K.D., Aisner, D.L., Pilling, A.B., Berge, E.M., Kim, J., Sasaki, H., Park, S., Kryukov, G., Garraway, L.A., Hammerman, Peter S., Haas, J., Andrews, S.W., Lipson, D., Stephens, P.J., Miller, V.A., Varella-Garcia, M., Jänne, P.A., Doebele, R.C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2013
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3823836/
https://www.ncbi.nlm.nih.gov/pubmed/24162815
http://dx.doi.org/10.1038/nm.3352
Descripción
Sumario:We identified novel gene fusions in patients with lung cancer harboring the kinase domain of the NTRK1 gene that encodes the TRKA receptor. Both the MPRIP-NTRK1 and CD74-NTRK1 fusions lead to constitutive TRKA kinase activity and are oncogenic. Treatment of cells expressing NTRK1 fusions with inhibitors of TRKA kinase activity inhibited autophosphorylation of TRKA and cell growth. Three of 91 lung cancer patients (3.3%), without known oncogenic alterations, assayed by NGS or FISH demonstrated evidence of NTRK1 gene fusions.

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