Oncogenic and drug-sensitive NTRK1 rearrangements in lung cancer

Nat Med. 2013 Nov;19(11):1469-1472. doi: 10.1038/nm.3352. Epub 2013 Oct 27.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Antigens, Differentiation, B-Lymphocyte / genetics
  • Cell Line, Tumor
  • Gene Rearrangement*
  • Histocompatibility Antigens Class II / genetics
  • Humans
  • In Situ Hybridization, Fluorescence
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / genetics*
  • Molecular Sequence Data
  • Oncogene Fusion*
  • Protein Kinase Inhibitors / pharmacology
  • Receptor, trkA / antagonists & inhibitors
  • Receptor, trkA / genetics*

Substances

  • Adaptor Proteins, Signal Transducing
  • Antigens, Differentiation, B-Lymphocyte
  • Histocompatibility Antigens Class II
  • M-RIP protein, human
  • Protein Kinase Inhibitors
  • invariant chain
  • Receptor, trkA

Associated data

  • GENBANK/KF724384
  • GENBANK/KF724385