Oncogenic and drug-sensitive NTRK1 rearrangements in lung cancer

Aria Vaishnavi, Marzia Capelletti, Anh T. Le, Severine Kako, Mohit Butaney, Dalia Ercan, Sakshi Mahale, Kurtis D. Davies, Dara L. Aisner, Amanda B. Pilling, Eamon M. Berge, Jhingook Kim, Hidefumi Sasaki, Seung Il Park, Gregory Kryukov, Levi A. Garraway, Peter S. Hammerman, Julia Haas, Steven W. Andrews, Doron LipsonPhilip J. Stephens, Vince A. Miller, Marileila Varella-Garcia, Pasi A. Jänne, Robert C. Doebele

Research output: Contribution to journalArticlepeer-review

508 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1469-1472
Number of pages4
JournalNature medicine
Volume19
Issue number11
DOIs
StatePublished - Nov 2013
Externally publishedYes

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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