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Nat Med DOI:10.1038/nm.3352

Oncogenic and drug-sensitive NTRK1 rearrangements in lung cancer.

Publication TypeJournal Article
Year of Publication2013
AuthorsVaishnavi, A, Capelletti, M, Le, AT, Kako, S, Butaney, M, Ercan, D, Mahale, S, Davies, KD, Aisner, DL, Pilling, AB, Berge, EM, Kim, J, Sasaki, H, Park, S-il, Kryukov, G, Garraway, LA, Hammerman, PS, Haas, J, Andrews, SW, Lipson, D, Stephens, PJ, Miller, VA, Varella-Garcia, M, Jänne, PA, Doebele, RC
JournalNat Med
Date Published2013 Nov
KeywordsAdaptor Proteins, Signal Transducing, Antigens, Differentiation, B-Lymphocyte, Cell Line, Tumor, Gene Rearrangement, Histocompatibility Antigens Class II, Humans, In Situ Hybridization, Fluorescence, Lung Neoplasms, Molecular Sequence Data, Oncogene Fusion, Protein Kinase Inhibitors, Receptor, trkA

We identified new gene fusions in patients with lung cancer harboring the kinase domain of the NTRK1 gene that encodes the high-affinity nerve growth factor receptor (TRKA protein). 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. Tumor samples from 3 of 91 patients with lung cancer (3.3%) without known oncogenic alterations assayed by next-generation sequencing or fluorescence in situ hybridization demonstrated evidence of NTRK1 gene fusions.


Alternate JournalNat. Med.
PubMed ID24162815
PubMed Central IDPMC3823836
Grant ListP50 CA058187 / CA / NCI NIH HHS / United States
UL1 TR000154 / TR / NCATS NIH HHS / United States
UL1 RR025780 / RR / NCRR NIH HHS / United States
K08 CA163677 / CA / NCI NIH HHS / United States
P30CA46934 / CA / NCI NIH HHS / United States
P30 CA046934 / CA / NCI NIH HHS / United States
P50 CA090578 / CA / NCI NIH HHS / United States
P50CA058187 / CA / NCI NIH HHS / United States
UL1 TR001082 / TR / NCATS NIH HHS / United States
K12 CA086913 / CA / NCI NIH HHS / United States