Oncogenic and drug-sensitive NTRK1 rearrangements in lung cancer
Menée sur des échantillons tumoraux prélevés sur 91 patients atteints d'un cancer du poumon, cette étude met en évidence, pour 3,3% des patients, la présence de fusions de gènes impliquant le gène NTRK1 et induisant une activité kinase du récepteur 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.