title: NTRK1 fusion in glioblastoma multiforme.
abstract: Glioblastoma multiforme (GBM) is the most aggressive form of brain tumor, yet with no targeted therapy with substantial survival benefit. Recent studies on solid tumors showed that fusion genes often play driver roles and are promising targets for pharmaceutical intervention. To survey potential fusion genes in GBMs, we analysed RNA-Seq data from 162 GBM patients available through The Cancer Genome Atlas (TCGA), and found that 3' exons of neurotrophic tyrosine kinase receptor type 1 (NTRK1, encoding TrkA) are fused to 5' exons of the genes that are highly expressed in neuronal tissues, neurofascin (NFASC) and brevican (BCAN). The fusions preserved both the transmembrane and kinase domains of NTRK1 in frame. NTRK1 is a mediator of the pro-survival signaling of nerve growth factor (NGF) and is a known oncogene, found commonly altered in human cancer. While GBMs largely lacked NTRK1 expression, the fusion-positive GBMs expressed fusion transcripts in high abundance, and showed elevated NTRK1-pathway activity. Lentiviral transduction of the NFASC-NTRK1 fusion gene in NIH 3T3 cells increased proliferation in vitro, colony formation in soft agar, and tumor formation in mice, suggesting the possibility that the fusion contributed to the initiation or maintenance of the fusion-positive GBMs, and therefore may be a rational drug target.
authors.affiliation: Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea; Institute for Refractory Cancer Research, Samsung Medical Center, Seoul, Korea; Samsung Advanced Institute of Technology, Samsung Electronics Co., Ltd., Seoul, Korea.
authors.forename: Jinkuk
authors.initials: J
authors.lastname: Kim
authors.affiliation: Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea; Institute for Refractory Cancer Research, Samsung Medical Center, Seoul, Korea; Graduate School of Health Science & Technology, Samsung Advanced Institute for Health Science & Technology, Seoul, Korea.
authors.forename: Yeri
authors.initials: Y
authors.lastname: Lee
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Cho
authors.affiliation: Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea; Institute for Refractory Cancer Research, Samsung Medical Center, Seoul, Korea; Graduate School of Health Science & Technology, Samsung Advanced Institute for Health Science & Technology, Seoul, Korea.
authors.forename: Hee-Jin
authors.initials: HJ
authors.lastname: Cho
authors.affiliation: Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea; Institute for Refractory Cancer Research, Samsung Medical Center, Seoul, Korea; Graduate School of Health Science & Technology, Samsung Advanced Institute for Health Science & Technology, Seoul, Korea.
authors.forename: Young-Eun
authors.initials: YE
authors.lastname: Lee
authors.affiliation: Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea; Institute for Refractory Cancer Research, Samsung Medical Center, Seoul, Korea; Graduate School of Health Science & Technology, Samsung Advanced Institute for Health Science & Technology, Seoul, Korea.
authors.forename: Jaeyeol
authors.initials: J
authors.lastname: An
authors.affiliation: Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea.
authors.forename: Gye-Hyun
authors.initials: GH
authors.lastname: Cho
authors.affiliation: Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea; Department of Pathology, School of Medicine, Sungkyunkwan University, Seoul, Korea.
authors.forename: Young-Hyeh
authors.initials: YH
authors.lastname: Ko
authors.affiliation: Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea; Institute for Refractory Cancer Research, Samsung Medical Center, Seoul, Korea; Graduate School of Health Science & Technology, Samsung Advanced Institute for Health Science & Technology, Seoul, Korea; Department of Anatomy and Cell Biology, School of Medicine, Sungkyunkwan University, Seoul, Korea.
authors.forename: Kyeung Min
authors.initials: KM
authors.lastname: Joo
authors.affiliation: Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea; Institute for Refractory Cancer Research, Samsung Medical Center, Seoul, Korea; Graduate School of Health Science & Technology, Samsung Advanced Institute for Health Science & Technology, Seoul, Korea; Department of Neurosurgery, School of Medicine, Sungkyunkwan University, Seoul, Korea.
authors.forename: Do-Hyun
authors.initials: DH
authors.lastname: Nam
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001932:Brain Neoplasms / Q000378:metabolism*; D058581:Brevican / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D063646:Carcinogenesis / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005909:Glioblastoma / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D009414:Nerve Growth Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015514:Oncogene Proteins, Fusion / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020917:Receptor, trkA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: C546938:BCAN protein, human; D058581:Brevican; D015815:Cell Adhesion Molecules; C054305:NFASC protein, human; D009414:Nerve Growth Factors; D015514:Oncogene Proteins, Fusion; C000593970:BCAN-NTRK1 fusion protein, human; C000593969:NFASC-NTRK1 fusion protein, human; D020917:Receptor, trkA