title: Oncogenic and drug-sensitive NTRK1 rearrangements in lung cancer.
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.
authors.affiliation: Division of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO.
authors.forename: A
authors.initials: A
authors.lastname: Vaishnavi
authors.affiliation: Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA.
authors.forename: M
authors.initials: M
authors.lastname: Capelletti
authors.affiliation: Division of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO.
authors.forename: A T
authors.initials: AT
authors.lastname: Le
authors.affiliation: University of Colorado Cancer Center, Aurora, CO.
authors.forename: S
authors.initials: S
authors.lastname: Kako
authors.affiliation: Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA.
authors.forename: M
authors.initials: M
authors.lastname: Butaney
authors.affiliation: Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA.
authors.forename: D
authors.initials: D
authors.lastname: Ercan
authors.affiliation: University of Colorado Cancer Center, Aurora, CO.
authors.forename: S
authors.initials: S
authors.lastname: Mahale
authors.affiliation: Division of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO.
authors.forename: K D
authors.initials: KD
authors.lastname: Davies
authors.affiliation: University of Colorado Cancer Center, Aurora, CO.|Department of Pathology, University of Colorado School of Medicine, Aurora, CO.
authors.forename: D L
authors.initials: DL
authors.lastname: Aisner
authors.affiliation: Division of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO.
authors.forename: A B
authors.initials: AB
authors.lastname: Pilling
authors.affiliation: Division of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO.
authors.forename: E M
authors.initials: EM
authors.lastname: Berge
authors.affiliation: Department of Thoracic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: J
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Sasaki
authors.affiliation: Department of Thoracic Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
authors.forename: S
authors.initials: S
authors.lastname: Park
authors.affiliation: Broad Institute, Cambridge, MA.
authors.forename: G
authors.initials: G
authors.lastname: Kryukov
authors.affiliation: Broad Institute, Cambridge, MA.|Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.
authors.forename: L A
authors.initials: LA
authors.lastname: Garraway
authors.affiliation: Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA.
authors.forename: Peter S
authors.initials: PS
authors.lastname: Hammerman
authors.affiliation: Array BioPharma, Boulder, CO.
authors.forename: J
authors.initials: J
authors.lastname: Haas
authors.affiliation: Array BioPharma, Boulder, CO.
authors.forename: S W
authors.initials: SW
authors.lastname: Andrews
authors.affiliation: Foundation Medicine, Inc., Boston, MA.
authors.forename: D
authors.initials: D
authors.lastname: Lipson
authors.affiliation: Foundation Medicine, Inc., Boston, MA.
authors.forename: P J
authors.initials: PJ
authors.lastname: Stephens
authors.affiliation: Foundation Medicine, Inc., Boston, MA.
authors.forename: V A
authors.initials: VA
authors.lastname: Miller
authors.affiliation: Division of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO.|University of Colorado Cancer Center, Aurora, CO.
authors.forename: M
authors.initials: M
authors.lastname: Varella-Garcia
authors.affiliation: Lowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA.|Belfer Institute for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, MA.
authors.forename: P A
authors.initials: PA
authors.lastname: Jänne
authors.affiliation: Division of Medical Oncology, Department of Medicine, University of Colorado School of Medicine, Aurora, CO.|University of Colorado Cancer Center, Aurora, CO.
authors.forename: R C
authors.initials: RC
authors.lastname: Doebele
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics; D045744:Cell Line, Tumor; D015321:Gene Rearrangement; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D008969:Molecular Sequence Data; D050596:Oncogene Fusion; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D020917:Receptor, trkA / Q000037:antagonists & inhibitors / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; C498552:MPRIP protein, human; D047428:Protein Kinase Inhibitors; C045084:invariant chain; D020917:Receptor, trkA