title: HIP1-ALK, a novel fusion protein identified in lung adenocarcinoma.
abstract: BACKGROUND
  The most common mechanism underlying overexpression and activation of anaplastic lymphoma kinase (ALK) in non-small-cell lung carcinoma could be attributed to the formation of a fusion protein. To date, five fusion partners of ALK have been reported, namely, echinoderm microtubule associated protein like 4, tropomyosin-related kinase-fused gene, kinesin family member 5B, kinesin light chain 1, and protein tyrosine phosphatase, nonreceptor type 3.
  
  
  METHODS
  In this article, we report a novel fusion gene huntingtin interacting protein 1 (HIP1)-ALK, which is conjoined between the huntingtin-interacting protein 1 gene HIP1 and ALK. Reverse-transcriptase polymerase chain reaction and immunohistochemical analysis were used to detect this fusion gene's transcript and protein expression, respectively. We had amplified the full-length cDNA sequence of this novel fusion gene by using 5'-rapid amplification of cDNA ends. The causative genomic translocation t(2;7)(p23;q11.23) for generating this novel fusion gene was verified by using genomic sequencing.
  
  
  RESULTS
  The examined adenocarcinoma showed predominant acinar pattern, and ALK immunostaining was localized to the cytoplasm, with intense staining in the submembrane region. In break-apart, fluorescence in situ hybridization analysis for ALK, split of the 5' and 3' probe signals, and isolated 3' signals were observed. Reverse-transcriptase polymerase chain reaction revealed that the tumor harbored a novel fusion transcript in which exon 21 of HIP1 was fused to exon 20 of ALK in-frame.
  
  
  CONCLUSIONS
  The novel fusion gene and its protein HIP1-ALK harboring epsin N-terminal homology, coiled-coil, juxtamembrane, and kinase domains, which could play a role in carcinogenesis, could become diagnostic and therapeutic target of the lung adenocarcinoma and deserve a further study in the future.
authors: Departments of *Pathology, §Thoracic Surgery, Samsung Medical Center, Sungkyunkwan University College of Medicine, Seoul, Korea; †Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul, Korea; ‡Laboratory of Cancer Genomics and Molecular Pathology, Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea; ‖Pfizer Oncology, San Diego, California; ¶Pathology Project for Molecular Targets of the Cancer Institute/Division of Pathology of the Cancer Institute Hospital, Japanese Foundation for Cancer Research, Tokyo, Japan; and #Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Mineui
authors: M
authors: Hong
authors: Ryong Nam
authors: RN
authors: Kim
authors: Ji-Young
authors: JY
authors: Song
authors: So-Jung
authors: SJ
authors: Choi
authors: Ensel
authors: E
authors: Oh
authors: Maruja E
authors: ME
authors: Lira
authors: Mao
authors: M
authors: Mao
authors: Kengo
authors: K
authors: Takeuchi
authors: Joungho
authors: J
authors: Han
authors: Jhingook
authors: J
authors: Kim
authors: Yoon-La
authors: YL
authors: Choi
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D000328:Adult; D000077548:Anaplastic Lymphoma Kinase; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014178:Translocation, Genetic
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; C073368:HIP1 protein, human; D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases