Molecules and Cells

  • 제41권5호
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  • Pages.465-475
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  • 2018
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  • 1016-8478(pISSN)
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  • 0219-1032(eISSN)
한국분자세포생물학회 (Korean Society for Molecular and Cellular Biology)
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Identification of Novel Functional Variants of SIN3A and SRSF1 among Somatic Variants in Acute Myeloid Leukemia Patients

  • Min, Jae-Woong (Division of Biomedical Convergence, College of Biomedical Science, Institute of Bioscience & Biotechnology, Kangwon National University) ;
  • Koh, Youngil (Department of Internal Medicine, Seoul National University Hospital) ;
  • Kim, Dae-Yoon (Cancer Research Institute, Seoul National University College of Medicine) ;
  • Kim, Hyung-Lae (Department of Biochemistry, School of Medicine, Ewha Woman's University) ;
  • Han, Jeong A (Department of Biochemistry and Molecular Biology, School of Medicine, Kangwon National University) ;
  • Jung, Yu-Jin (Department of Biological Sciences, Kangwon National University) ;
  • Yoon, Sung-Soo (Department of Internal Medicine, Seoul National University Hospital) ;
  • Choi, Sun Shim (Division of Biomedical Convergence, College of Biomedical Science, Institute of Bioscience & Biotechnology, Kangwon National University)
  • 투고 : 2018.01.29
  • 심사 : 2018.03.08
  • 발행 : 2018.05.31
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초록

The advent of massively parallel sequencing, also called next-generation sequencing (NGS), has dramatically influenced cancer genomics by accelerating the identification of novel molecular alterations. Using a whole genome sequencing (WGS) approach, we identified somatic coding and noncoding variants that may contribute to leukemogenesis in 11 adult Korean acute myeloid leukemia (AML) patients, with serial tumor samples (primary and relapse) available for 5 of them; somatic variants were identified in 187 AML-related genes, including both novel (SIN3A, C10orf53, PTPRR, and RERGL) and well-known (NPM1, RUNX1, and CEPBA) AML-related genes. Notably, SIN3A expression shows prognostic value in AML. A newly designed method, referred to as "hot-zone" analysis, detected two putative functional noncoding variants that can alter transcription factor binding affinity near PPP1R10 and SRSF1. Moreover, the functional importance of the SRSF1 noncoding variant was further investigated by luciferase assays, which showed that the variant is critical for the regulation of gene expression leading to leukemogenesis. We expect that further functional investigation of these coding and noncoding variants will contribute to a more in-depth understanding of the underlying molecular mechanisms of AML and the development of targeted anti-cancer drugs.

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