Discovery of ALK-PTPN3 gene fusion from human non-small cell lung carcinoma cell line using next generation RNA sequencing

Authors

  • Yeonjoo Jung,

    1. Ewha Research Center for Systems Biology, Seoul, Korea
    2. Division of Life and Pharmaceutical Sciences and the Center for Cell Signaling and Drug Discovery Research, Ewha Woman's University, Seoul, Korea
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    • These authors contributed equally to this work.

  • Pora Kim,

    1. Ewha Research Center for Systems Biology, Seoul, Korea
    2. Division of Life and Pharmaceutical Sciences and the Center for Cell Signaling and Drug Discovery Research, Ewha Woman's University, Seoul, Korea
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    • These authors contributed equally to this work.

  • Yeonhwa Jung,

    1. Ewha Research Center for Systems Biology, Seoul, Korea
    2. Division of Life and Pharmaceutical Sciences and the Center for Cell Signaling and Drug Discovery Research, Ewha Woman's University, Seoul, Korea
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  • Juhee Keum,

    1. Ewha Research Center for Systems Biology, Seoul, Korea
    2. Division of Life and Pharmaceutical Sciences and the Center for Cell Signaling and Drug Discovery Research, Ewha Woman's University, Seoul, Korea
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  • Soon-Nam Kim,

    1. Ewha Research Center for Systems Biology, Seoul, Korea
    2. Division of Life and Pharmaceutical Sciences and the Center for Cell Signaling and Drug Discovery Research, Ewha Woman's University, Seoul, Korea
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  • Yong Soo Choi,

    1. Department of Thoracic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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  • In-Gu Do,

    1. Experimental Pathology Center, Samsung Cancer Research Institute, Samsung Medical Center, Seoul, Korea
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  • Jinseon Lee,

    1. Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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  • So-Jung Choi,

    1. Samsung Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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  • Sujin Kim,

    1. DNA Link, Inc., Seoul, Korea
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  • Jong-Eun Lee,

    1. DNA Link, Inc., Seoul, Korea
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  • Jhingook Kim,

    1. Department of Thoracic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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  • Sanghyuk Lee,

    Corresponding author
    1. Ewha Research Center for Systems Biology, Seoul, Korea
    2. Division of Life and Pharmaceutical Sciences and the Center for Cell Signaling and Drug Discovery Research, Ewha Woman's University, Seoul, Korea
    3. Korean Bioinformation Center, Daejeon, Korea
    • Division of Life and Pharmaceutical Sciences and the Center for Cell Signaling and Drug Discovery Research, Ewha Woman's University, Science Bldg C-518, Seoul, Korea 120-750
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  • Jaesang Kim

    Corresponding author
    1. Ewha Research Center for Systems Biology, Seoul, Korea
    2. Division of Life and Pharmaceutical Sciences and the Center for Cell Signaling and Drug Discovery Research, Ewha Woman's University, Seoul, Korea
    • Division of Life and Pharmaceutical Sciences and the Center for Cell Signaling and Drug Discovery Research, Ewha Woman's University, Science Bldg C-406, Seoul, Korea 120-750
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Abstract

An increasing number of chromosomal aberrations is being identified in solid tumors providing novel biomarkers for various types of cancer and new insights into the mechanisms of carcinogenesis. We applied next generation sequencing technique to analyze the transcriptome of the non-small cell lung carcinoma (NSCLC) cell line H2228 and discovered a fusion transcript composed of multiple exons of ALK (anaplastic lymphoma receptor tyrosine kinase) and PTPN3 (protein tyrosine phosphatase, nonreceptor Type 3). Detailed analysis of the genomic structure revealed that a portion of genomic region encompassing Exons 10 and 11 of ALK has been translocated into the intronic region between Exons 2 and 3 of PTPN3. The key net result appears to be the null mutation of one allele of PTPN3, a gene with tumor suppressor activity. Consistently, ectopic expression of PTPN3 in NSCLC cell lines led to inhibition of colony formation. Our study confirms the utility of next generation sequencing as a tool for the discovery of somatic mutations and has led to the identification of a novel mutation in NSCLC that may be of diagnostic, prognostic, and therapeutic importance. © 2012 Wiley Periodicals, Inc.

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