title: A novel fusion of TPR and ALK in lung adenocarcinoma.
abstract: BACKGROUND
  Anaplastic lymphoma kinase (ALK) fusion is the most common mechanism for overexpression and activation in non-small-cell lung carcinoma. Several fusion partners of ALK have been reported, including echinoderm microtubule-associated protein-like 4, TRK-fused gene, kinesin family member 5B, kinesin light chain 1 (KLC1), protein tyrosine phosphatase and nonreceptor type 3, and huntingtin interacting protein 1 (HIP1).
  
  
  RESULTS
  A 60-year-old Korean man had a lung mass which was a poorly differentiated adenocarcinoma with ALK overexpression. By using an Anchored Multiplex polymerase chain reaction assay and sequencing, we found that tumor had a novel translocated promoter region (TPR)-ALK fusion. The fusion transcript was generated from an intact, in-frame fusion of TPR exon 15 and ALK exon 20 (t(1;2)(q31.1;p23)). The TPR-ALK fusion encodes a predicted protein of 1192 amino acids with a coiled-coil domain encoded by the 5'-2 of the TPR and juxtamembrane and kinase domains encoded by the 3'-end of the ALK.
  
  
  CONCLUSIONS
  The novel fusion gene and its protein TRP-ALK, harboring coiled-coil and kinase domains, could possess transforming potential and responses to treatment with ALK inhibitors. This case is the first report of TPR-ALK fusion transcript in clinical tumor samples and could provide a novel diagnostic and therapeutic candidate target for patients with cancer, including non-small-cell lung carcinoma.
authors.affiliation: Departments of *Pathology and **Thoracic Surgery, Samsung Medical Center, Sungkyunkwan University College of Medicine, Seoul, Korea; †Laboratory of Cancer Genomics and Molecular Pathology, Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea; ‡Oncology Research Unit, Pfizer Inc., San Diego, California; §Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul, Korea; ‖ArcherDx Inc., Boulder, Colorado; ¶Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts; and #Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Yoon-La
authors.initials: YL
authors.lastname: Choi
authors.forename: Maruja E
authors.initials: ME
authors.lastname: Lira
authors.forename: Mineui
authors.initials: M
authors.lastname: Hong
authors.forename: Ryong Nam
authors.initials: RN
authors.lastname: Kim
authors.forename: So-Jung
authors.initials: SJ
authors.lastname: Choi
authors.forename: Ji-Young
authors.initials: JY
authors.lastname: Song
authors.forename: Kinnari
authors.initials: K
authors.lastname: Pandy
authors.forename: Derrick L
authors.initials: DL
authors.lastname: Mann
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Stahl
authors.forename: Heather E
authors.initials: HE
authors.lastname: Peckham
authors.forename: Zongli
authors.initials: Z
authors.lastname: Zheng
authors.forename: Joungho
authors.initials: J
authors.lastname: Han
authors.forename: Mao
authors.initials: M
authors.lastname: Mao
authors.forename: Jhingook
authors.initials: J
authors.lastname: Kim
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D000077548:Anaplastic Lymphoma Kinase; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D005091:Exons / Q000235:genetics; D015321:Gene Rearrangement; D006801:Humans; D016547:Kinesins; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D028861:Nuclear Pore Complex Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D014178:Translocation, Genetic / Q000235:genetics*
chemical_list: C000715688:KLC1 protein, human; D028861:Nuclear Pore Complex Proteins; D015514:Oncogene Proteins, Fusion; D011518:Proto-Oncogene Proteins; C073597:TPR protein, human; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases; D016547:Kinesins