Oncogenic and drug-sensitive NTRK1 rearrangements in lung cancer.

Autor: Vaishnavi A; Division of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO., Capelletti M; Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA., Le AT; Division of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO., Kako S; University of Colorado Cancer Center, Aurora, CO., Butaney M; Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA., Ercan D; Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA., Mahale S; University of Colorado Cancer Center, Aurora, CO., Davies KD; Division of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO., Aisner DL; University of Colorado Cancer Center, Aurora, CO.; Department of Pathology, University of Colorado School of Medicine, Aurora, CO., Pilling AB; Division of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO., Berge EM; Division of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO., Kim J; Department of Thoracic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea., Sasaki H; Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan., Park S; Department of Thoracic Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea., Kryukov G; Broad Institute, Cambridge, MA., Garraway LA; Broad Institute, Cambridge, MA.; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA., Hammerman PS; Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA., Haas J; Array BioPharma, Boulder, CO., Andrews SW; Array BioPharma, Boulder, CO., Lipson D; Foundation Medicine, Inc., Boston, MA., Stephens PJ; Foundation Medicine, Inc., Boston, MA., Miller VA; Foundation Medicine, Inc., Boston, MA., Varella-Garcia M; Division of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO.; University of Colorado Cancer Center, Aurora, CO., Jänne PA; Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA.; Belfer Institute for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, MA., Doebele RC; Division of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO.; University of Colorado Cancer Center, Aurora, CO.
Jazyk: angličtina
Zdroj: Nature medicine [Nat Med] 2013 Nov; Vol. 19 (11), pp. 1469-1472. Date of Electronic Publication: 2013 Oct 27.
DOI: 10.1038/nm.3352
Abstrakt: 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.
Databáze: MEDLINE