RESUMO

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.

Assuntos

Rearranjo Gênico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Fusão Oncogênica , Receptor trkA/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Antígenos de Diferenciação de Linfócitos B/genética , Linhagem Celular Tumoral , Antígenos de Histocompatibilidade Classe II/genética , Humanos , Hibridização in Situ Fluorescente , Dados de Sequência Molecular , Inibidores de Proteínas Quinases/farmacologia , Receptor trkA/antagonistas & inibidores